rs113993989

Positions:

chr7-66994329-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_016038.4(SBDS):c.141C>T(p.Leu47Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00452 in 1,612,664 control chromosomes in the GnomAD database, including 45 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0076 ( 9 hom., cov: 32)

Exomes 𝑓: 0.0042 ( 36 hom. )

Consequence

SBDS
NM_016038.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.801

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 links:

SBDS (HGNC:):

SBDS links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 7-66994329-G-A is Benign according to our data. Variant chr7-66994329-G-A is described in ClinVar as [Benign]. Clinvar id is 21536.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-66994329-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.801 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00765 (1163/152066) while in subpopulation EAS AF= 0.0334 (173/5182). AF 95% confidence interval is 0.0293. There are 9 homozygotes in gnomad4. There are 590 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 9 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SBDS	NM_016038.4 linkuse as main transcript	c.141C>T	p.Leu47Leu	synonymous_variant	2/5	ENST00000246868.7	NP_057122.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SBDS	ENST00000246868.7 linkuse as main transcript	c.141C>T	p.Leu47Leu	synonymous_variant	2/5	1	NM_016038.4	ENSP00000246868.2		Q9Y3A5

Frequencies

GnomAD3 genomes

AF:

0.00763

AC:

1159

AN:

151950

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00427

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.0333

Gnomad SAS

AF:

0.00831

Gnomad FIN

AF:

0.00397

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00447

Gnomad OTH

AF:

0.0115

GnomAD3 exomes

AF:

0.00653

AC:

1641

AN:

251316

Hom.:

AF XY:

0.00599

AC XY:

814

AN XY:

135840

show subpopulations

Gnomad AFR exome

AF:

0.0126

Gnomad AMR exome

AF:

0.00309

Gnomad ASJ exome

AF:

0.00258

Gnomad EAS exome

AF:

0.0336

Gnomad SAS exome

AF:

0.00546

Gnomad FIN exome

AF:

0.00343

Gnomad NFE exome

AF:

0.00361

Gnomad OTH exome

AF:

0.00538

GnomAD4 exome

AF:

0.00419

AC:

6123

AN:

1460598

Hom.:

Cov.:

AF XY:

0.00422

AC XY:

3065

AN XY:

726670

show subpopulations

Gnomad4 AFR exome

AF:

0.0105

Gnomad4 AMR exome

AF:

0.00333

Gnomad4 ASJ exome

AF:

0.00237

Gnomad4 EAS exome

AF:

0.0250

Gnomad4 SAS exome

AF:

0.00584

Gnomad4 FIN exome

AF:

0.00305

Gnomad4 NFE exome

AF:

0.00309

Gnomad4 OTH exome

AF:

0.00630

GnomAD4 genome

AF:

0.00765

AC:

1163

AN:

152066

Hom.:

Cov.:

AF XY:

0.00794

AC XY:

590

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.0121

Gnomad4 AMR

AF:

0.00426

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.0334

Gnomad4 SAS

AF:

0.00832

Gnomad4 FIN

AF:

0.00397

Gnomad4 NFE

AF:

0.00447

Gnomad4 OTH

AF:

0.0118

Alfa

AF:

0.00478

Hom.:

Bravo

AF:

0.00747

EpiCase

AF:

0.00486

EpiControl

AF:

0.00362

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Sep 01, 2024	SBDS: BP4, BP7, BS1, BS2 -

Shwachman-Diamond syndrome 1

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	Jul 28, 2017	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	Jul 20, 2016	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 31, 2017

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

-0.52

CADD

Benign

6.7

DANN

Benign

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over