rs73151675

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

2

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]

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
SBDSNM_016038.4 linkuse as main transcriptc.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
SBDSENST00000246868.7 linkuse as main transcriptc.651C>T p.Phe217= synonymous_variant 5/51 NM_016038.4 ENSP00000246868 P1

Frequencies

GnomAD3 genomes
AF:
0.0359
AC:
5452
AN:
152036
Hom.:
136
Cov.:
32
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.:
31
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.:
32
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:
31
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 submitterclinical testingARUP Laboratories, Molecular Genetics and Genomics, ARUP LaboratoriesMar 29, 2017- -
Benign, criteria provided, single submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineMar 29, 2016Variant 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 submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
not provided Benign:2
Benign, criteria provided, single submitterclinical testingGeneDxMar 03, 2015- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Inborn genetic diseases Benign:1
Benign, criteria provided, single submitterclinical testingAmbry GeneticsFeb 09, 2016This 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 submitterclinical testingKCCC/NGS Laboratory, Kuwait Cancer Control CenterJul 07, 2023- -

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

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

Other links and lift over

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