chr7-66994269-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_016038.4(SBDS):c.201A>G(p.Lys67Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0994 in 1,611,710 control chromosomes in the GnomAD database, including 9,317 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.085 ( 772 hom., cov: 32)

Exomes 𝑓: 0.10 ( 8545 hom. )

Consequence

SBDS
NM_016038.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 1.61

Publications

20 publications found

Variant links:

Genes affected

SBDS (HGNC:19440): (SBDS ribosome maturation factor) This gene encodes a highly conserved protein that plays an essential role in ribosome biogenesis. The encoded protein interacts with elongation factor-like GTPase 1 to disassociate eukaryotic initiation factor 6 from the late cytoplasmic pre-60S ribosomal subunit allowing assembly of the 80S subunit. Mutations within this gene are associated with the autosomal recessive disorder Shwachman-Bodian-Diamond syndrome. This gene has a closely linked pseudogene that is distally located. [provided by RefSeq, Jan 2017]

SBDS Gene-Disease associations (from GenCC):

Shwachman-Diamond syndrome
Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
Shwachman-Diamond syndrome 1
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia

SBDS links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 7-66994269-T-C is Benign according to our data. Variant chr7-66994269-T-C is described in ClinVar as Benign. ClinVar VariationId is 21537.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.61 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SBDS	NM_016038.4 link	c.201A>G	p.Lys67Lys	synonymous_variant	Exon 2 of 5	ENST00000246868.7	NP_057122.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SBDS	ENST00000246868.7 link	c.201A>G	p.Lys67Lys	synonymous_variant	Exon 2 of 5	1	NM_016038.4	ENSP00000246868.2		Q9Y3A5

Frequencies

GnomAD3 genomes

AF:

0.0846

AC:

12866

AN:

152056

Hom.:

771

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0261

Gnomad AMI

AF:

0.0471

Gnomad AMR

AF:

0.0853

Gnomad ASJ

AF:

0.102

Gnomad EAS

AF:

0.00366

Gnomad SAS

AF:

0.0336

Gnomad FIN

AF:

0.220

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.108

Gnomad OTH

AF:

0.101

GnomAD2 exomes

AF:

0.0874

AC:

21958

AN:

251294

AF XY:

0.0873

show subpopulations

Gnomad AFR exome

AF:

0.0233

Gnomad AMR exome

AF:

0.0601

Gnomad ASJ exome

AF:

0.103

Gnomad EAS exome

AF:

0.00321

Gnomad FIN exome

AF:

0.215

Gnomad NFE exome

AF:

0.106

Gnomad OTH exome

AF:

0.0987

GnomAD4 exome

AF:

0.101

AC:

147396

AN:

1459538

Hom.:

8545

Cov.:

AF XY:

0.0991

AC XY:

71949

AN XY:

726206

show subpopulations

African (AFR)

AF:

0.0207

AC:

694

AN:

33452

American (AMR)

AF:

0.0627

AC:

2801

AN:

44688

Ashkenazi Jewish (ASJ)

AF:

0.105

AC:

2733

AN:

26122

East Asian (EAS)

AF:

0.00247

AC:

AN:

39664

South Asian (SAS)

AF:

0.0359

AC:

3092

AN:

86208

European-Finnish (FIN)

AF:

0.209

AC:

11145

AN:

53390

Middle Eastern (MID)

AF:

0.0699

AC:

403

AN:

5762

European-Non Finnish (NFE)

AF:

0.109

AC:

120919

AN:

1109918

Other (OTH)

AF:

0.0913

AC:

5511

AN:

60334

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

Heterozygous variant carriers

6588

13175

19763

26350

32938

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4352

8704

13056

17408

21760

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0846

AC:

12868

AN:

152172

Hom.:

772

Cov.:

AF XY:

0.0881

AC XY:

6553

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.0261

AC:

1085

AN:

41546

American (AMR)

AF:

0.0852

AC:

1302

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.102

AC:

355

AN:

3472

East Asian (EAS)

AF:

0.00367

AC:

AN:

5178

South Asian (SAS)

AF:

0.0334

AC:

161

AN:

4824

European-Finnish (FIN)

AF:

0.220

AC:

2327

AN:

10572

Middle Eastern (MID)

AF:

0.0850

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.108

AC:

7342

AN:

67976

Other (OTH)

AF:

0.0991

AC:

209

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

578

1156

1733

2311

2889

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

142

284

426

568

710

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0941

Hom.:

676

Bravo

AF:

0.0731

Asia WGS

AF:

0.0180

AC:

AN:

3478

EpiCase

AF:

0.108

EpiControl

AF:

0.103

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Dec 05, 2016

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Shwachman-Diamond syndrome 1

Benign:2

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 07, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Aplastic anemia

Benign:1

Feb 01, 2025

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Inborn genetic diseases

Benign:1

Sep 11, 2017

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Benign

0.81

PhyloP100

1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over