rs140651555

Positions:

chr2-73847510-G-A

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_StrongBP6BS1

The NM_213622.4(STAMBP):c.499G>A(p.Glu167Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000251 in 1,614,182 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00015 ( 1 hom. )

Consequence

STAMBP
NM_213622.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 5.09

Variant links:

Genes affected

STAMBP (HGNC:16950): (STAM binding protein) Cytokine-mediated signal transduction in the JAK-STAT cascade requires the involvement of adaptor molecules. One such signal-transducing adaptor molecule contains an SH3 domain that is required for induction of MYC and cell growth. The protein encoded by this gene binds to the SH3 domain of the signal-transducing adaptor molecule, and plays a critical role in cytokine-mediated signaling for MYC induction and cell cycle progression. Multiple alternatively spliced transcript variants encoding the same protein isoform have been found for this gene. [provided by RefSeq, Jul 2008]

STAMBP links:

STAMBP (HGNC:):

STAMBP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.008151978).

BP6

Variant 2-73847510-G-A is Benign according to our data. Variant chr2-73847510-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 160045.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00119 (181/152352) while in subpopulation AFR AF= 0.00421 (175/41576). AF 95% confidence interval is 0.0037. There are 0 homozygotes in gnomad4. There are 86 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STAMBP	NM_213622.4 linkuse as main transcript	c.499G>A	p.Glu167Lys	missense_variant	5/10	ENST00000394070.7	NP_998787.1	O95630-1A0A140VK54

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STAMBP	ENST00000394070.7 linkuse as main transcript	c.499G>A	p.Glu167Lys	missense_variant	5/10	1	NM_213622.4	ENSP00000377633.2		O95630-1

Frequencies

GnomAD3 genomes

AF:

0.00119

AC:

181

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00422

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000288

AC:

AN:

250130

Hom.:

AF XY:

0.000229

AC XY:

AN XY:

135284

show subpopulations

Gnomad AFR exome

AF:

0.00415

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000355

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000153

AC:

224

AN:

1461830

Hom.:

Cov.:

AF XY:

0.000144

AC XY:

105

AN XY:

727218

show subpopulations

Gnomad4 AFR exome

AF:

0.00493

Gnomad4 AMR exome

AF:

0.0000894

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000342

Gnomad4 OTH exome

AF:

0.000281

GnomAD4 genome

AF:

0.00119

AC:

181

AN:

152352

Hom.:

Cov.:

AF XY:

0.00115

AC XY:

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.00421

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000322

Hom.:

Bravo

AF:

0.00147

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00522

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000362

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Microcephaly-capillary malformation syndrome

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Dec 11, 2013

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 11, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

T;T;.;T;T;.

Eigen

Benign

-0.13

Eigen_PC

Benign

0.015

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.89

.;D;D;.;.;D

M_CAP

Benign

0.0070

MetaRNN

Benign

0.0082

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.4

M;M;.;M;M;.

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-1.8

N;N;N;N;N;N

REVEL

Benign

0.13

Sift

Benign

0.085

T;T;T;T;T;T

Sift4G

Benign

0.40

T;T;T;T;T;D

Polyphen

0.0

B;B;.;B;B;.

Vest4

0.19

MVP

0.61

MPC

0.35

ClinPred

0.055

GERP RS

4.0

Varity_R

0.15

gMVP

0.51

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