rs1061695

chr7-66994269-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_016038.4(SBDS):c.201A>G(p.Lys67=) 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 1.61

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 -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 id is 21537.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-66994269-T-C is described in Lovd as [Benign].
• 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/exons	MANE	UniProt
SBDS	NM_016038.4	c.201A>G	p.Lys67=	synonymous_variant	2/5	ENST00000246868.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SBDS	ENST00000246868.7	c.201A>G	p.Lys67=	synonymous_variant	2/5	1	NM_016038.4	P1

Frequencies

GnomAD3 genomes AF: 0.0846 AC: 12866 AN: 152056 Hom.: 771 Cov.: 32

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

GnomAD3 exomes AF: 0.0874 AC: 21958 AN: 251294 Hom.: 1387 AF XY: 0.0873 AC XY: 11853 AN XY: 135822

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 SAS exome AF: 0.0362

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.: 32 AF XY: 0.0991 AC XY: 71949 AN XY: 726206

Gnomad4 AFR exome AF: 0.0207

Gnomad4 AMR exome AF: 0.0627

Gnomad4 ASJ exome AF: 0.105

Gnomad4 EAS exome AF: 0.00247

Gnomad4 SAS exome AF: 0.0359

Gnomad4 FIN exome AF: 0.209

Gnomad4 NFE exome AF: 0.109

Gnomad4 OTH exome AF: 0.0913

GnomAD4 genome AF: 0.0846 AC: 12868 AN: 152172 Hom.: 772 Cov.: 32 AF XY: 0.0881 AC XY: 6553 AN XY: 74388

Gnomad4 AFR AF: 0.0261

Gnomad4 AMR AF: 0.0852

Gnomad4 ASJ AF: 0.102

Gnomad4 EAS AF: 0.00367

Gnomad4 SAS AF: 0.0334

Gnomad4 FIN AF: 0.220

Gnomad4 NFE AF: 0.108

Gnomad4 OTH AF: 0.0991

Alfa AF: 0.0955 Hom.: 332

Bravo AF: 0.0731

Asia WGS AF: 0.0180 AC: 65 AN: 3478

EpiCase AF: 0.108

EpiControl AF: 0.103

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Dec 05, 2016	- -

Shwachman-Diamond syndrome 1 Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Nov 07, 2021	- -
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

Sep 11, 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. -

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	-0.58
Cadd	Benign	15
Dann	Benign	0.81
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

LitVar

Other links and lift over

dbSNP: rs1061695; hg19: chr7-66459256; COSMIC: COSV55887570; COSMIC: COSV55887570;