rs73151675

Variant names:

• chr7-66988473-G-A
• rs73151675
• NM_016038.4:c.651C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_016038.4(SBDS):​c.651C>T​(p.Phe217Phe) 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:8
• Conservation: PhyloP100: 5.24
• Publications: 7 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
SBDS	NM_016038.4	c.651C>T	p.Phe217Phe	synonymous_variant	Exon 5 of 5	ENST00000246868.7	NP_057122.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SBDS	ENST00000246868.7	c.651C>T	p.Phe217Phe	synonymous_variant	Exon 5 of 5	1	NM_016038.4	ENSP00000246868.2

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

GnomAD2 exomes AF: 0.0386 AC: 9710 AN: 251264 AF XY: 0.0390

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 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

African (AFR) AF: 0.00723 AC: 242 AN: 33480

American (AMR) AF: 0.0254 AC: 1138 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0718 AC: 1876 AN: 26136

East Asian (EAS) AF: 0.00176 AC: 70 AN: 39698

South Asian (SAS) AF: 0.00877 AC: 756 AN: 86252

European-Finnish (FIN) AF: 0.0496 AC: 2638 AN: 53140

Middle Eastern (MID) AF: 0.0160 AC: 92 AN: 5764

European-Non Finnish (NFE) AF: 0.0576 AC: 64094 AN: 1111878

Other (OTH) AF: 0.0473 AC: 2859 AN: 60384

GnomAD4 genome AF: 0.0358 AC: 5452 AN: 152154 Hom.: 136 Cov.: 32 AF XY: 0.0342 AC XY: 2541 AN XY: 74382

African (AFR) AF: 0.00951 AC: 395 AN: 41514

American (AMR) AF: 0.0287 AC: 438 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.0663 AC: 230 AN: 3470

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5184

South Asian (SAS) AF: 0.00831 AC: 40 AN: 4816

European-Finnish (FIN) AF: 0.0542 AC: 574 AN: 10582

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0539 AC: 3667 AN: 68016

Other (OTH) AF: 0.0307 AC: 65 AN: 2114

Alfa AF: 0.0467 Hom.: 126

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:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Mar 29, 2017

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Shwachman-Diamond syndrome 1 Benign:1

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Inborn genetic diseases Benign:1

Feb 09, 2016

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	-0.47
CADD	Benign	12
DANN	Benign	0.77
PhyloP100		5.2
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

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