Variant 7-66988473-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_016038.4(SBDS):c.651C>T(p.Phe217=) variant causes a synonymous change. The variant allele was found at a frequency of 0.0491 in 1,613,608 control chromosomes in the GnomAD database, including 2,252 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.036 ( 136 hom., cov: 32)

Exomes 𝑓: 0.050 ( 2116 hom. )

Consequence

SBDS
NM_016038.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 5.24

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 7-66988473-G-A is Benign according to our data. Variant chr7-66988473-G-A is described in ClinVar as [Benign]. Clinvar id is 21544.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0525 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SBDS	NM_016038.4 linkuse as main transcript	c.651C>T	p.Phe217=	synonymous_variant	5/5	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.651C>T	p.Phe217=	synonymous_variant	5/5	1	NM_016038.4	ENSP00000246868	P1

Frequencies

GnomAD3 genomes

AF:

0.0359

AC:

5452

AN:

152036

Hom.:

136

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00954

Gnomad AMI

AF:

0.0351

Gnomad AMR

AF:

0.0288

Gnomad ASJ

AF:

0.0663

Gnomad EAS

AF:

0.00115

Gnomad SAS

AF:

0.00830

Gnomad FIN

AF:

0.0542

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0539

Gnomad OTH

AF:

0.0311

GnomAD3 exomes

AF:

0.0386

AC:

9710

AN:

251264

Hom.:

273

AF XY:

0.0390

AC XY:

5300

AN XY:

135836

show subpopulations

Gnomad AFR exome

AF:

0.00781

Gnomad AMR exome

AF:

0.0235

Gnomad ASJ exome

AF:

0.0708

Gnomad EAS exome

AF:

0.000435

Gnomad SAS exome

AF:

0.00892

Gnomad FIN exome

AF:

0.0528

Gnomad NFE exome

AF:

0.0556

Gnomad OTH exome

AF:

0.0518

GnomAD4 exome

AF:

0.0505

AC:

73765

AN:

1461454

Hom.:

2116

Cov.:

AF XY:

0.0498

AC XY:

36211

AN XY:

727054

show subpopulations

Gnomad4 AFR exome

AF:

0.00723

Gnomad4 AMR exome

AF:

0.0254

Gnomad4 ASJ exome

AF:

0.0718

Gnomad4 EAS exome

AF:

0.00176

Gnomad4 SAS exome

AF:

0.00877

Gnomad4 FIN exome

AF:

0.0496

Gnomad4 NFE exome

AF:

0.0576

Gnomad4 OTH exome

AF:

0.0473

GnomAD4 genome

AF:

0.0358

AC:

5452

AN:

152154

Hom.:

136

Cov.:

AF XY:

0.0342

AC XY:

2541

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.00951

Gnomad4 AMR

AF:

0.0287

Gnomad4 ASJ

AF:

0.0663

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.00831

Gnomad4 FIN

AF:

0.0542

Gnomad4 NFE

AF:

0.0539

Gnomad4 OTH

AF:

0.0307

Alfa

AF:

0.0485

Hom.:

105

Bravo

AF:

0.0344

Asia WGS

AF:

0.00895

AC:

AN:

3478

EpiCase

AF:

0.0549

EpiControl

AF:

0.0540

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Mar 29, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 09, 2016

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. -

Shwachman-Diamond syndrome 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 07, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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