rs73151675

chr7-66988473-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 5.24

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]

ACMG classification

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	UniProt
SBDS	NM_016038.4	c.651C>T	p.Phe217=	synonymous_variant	5/5	ENST00000246868.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SBDS	ENST00000246868.7	c.651C>T	p.Phe217=	synonymous_variant	5/5	1	NM_016038.4	P1

Frequencies

GnomAD3 genomes AF: 0.0359 AC: 5452 AN: 152036 Hom.: 136 Cov.: 32

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

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.: 31 AF XY: 0.0498 AC XY: 36211 AN XY: 727054

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.: 32 AF XY: 0.0342 AC XY: 2541 AN XY: 74382

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: 31 AN: 3478

EpiCase AF: 0.0549

EpiControl AF: 0.0540

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

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	-	- -

Shwachman-Diamond syndrome 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 07, 2023

- -

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. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
Cadd	Benign	12
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

Other links and lift over

dbSNP: rs73151675; hg19: chr7-66453460; COSMIC: COSV55887114; COSMIC: COSV55887114;