Variant chr20-1578547-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006065.5(SIRPB1):c.224G>A(p.Arg75Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000391 in 1,583,686 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000041 ( 0 hom., cov: 29)

Exomes 𝑓: 0.000039 ( 0 hom. )

Consequence

SIRPB1
NM_006065.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.369

Variant links:

Genes affected

SIRPB1 (HGNC:15928): (signal regulatory protein beta 1) The protein encoded by this gene is a member of the signal-regulatory-protein (SIRP) family, and also belongs to the immunoglobulin superfamily. SIRP family members are receptor-type transmembrane glycoproteins known to be involved in the negative regulation of receptor tyrosine kinase-coupled signaling processes. This protein was found to interact with TYROBP/DAP12, a protein bearing immunoreceptor tyrosine-based activation motifs. This protein was also reported to participate in the recruitment of tyrosine kinase SYK. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2009]

SIRPB1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16323552).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SIRPB1	NM_006065.5 linkuse as main transcript	c.224G>A	p.Arg75Gln	missense_variant	2/6	ENST00000381605.9
SIRPB1	NM_001083910.4 linkuse as main transcript	c.224G>A	p.Arg75Gln	missense_variant	2/4
SIRPB1	NM_001330639.2 linkuse as main transcript	c.221G>A	p.Arg74Gln	missense_variant	2/4
SIRPB1	XM_005260641.4 linkuse as main transcript	c.221G>A	p.Arg74Gln	missense_variant	2/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIRPB1	ENST00000381605.9 linkuse as main transcript	c.224G>A	p.Arg75Gln	missense_variant	2/6	1	NM_006065.5		O00241-1

Frequencies

GnomAD3 genomes

AF:

0.0000408

AC:

AN:

146880

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.000848

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000152

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000444

AC:

AN:

247826

Hom.:

AF XY:

0.0000747

AC XY:

AN XY:

133946

show subpopulations

Gnomad AFR exome

AF:

0.0000618

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000295

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000390

AC:

AN:

1436806

Hom.:

Cov.:

AF XY:

0.0000518

AC XY:

AN XY:

714958

show subpopulations

Gnomad4 AFR exome

AF:

0.0000601

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000525

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000458

Gnomad4 OTH exome

AF:

0.0000336

GnomAD4 genome

AF:

0.0000408

AC:

AN:

146880

Hom.:

Cov.:

AF XY:

0.0000701

AC XY:

AN XY:

71342

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.000848

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000152

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000843

Hom.:

ExAC

AF:

0.0000582

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3468

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 02, 2021

The c.224G>A (p.R75Q) alteration is located in exon 2 (coding exon 2) of the SIRPB1 gene. This alteration results from a G to A substitution at nucleotide position 224, causing the arginine (R) at amino acid position 75 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

1.0

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.54

FATHMM_MKL

Benign

0.017

LIST_S2

Uncertain

0.91

D;D;D;D;D;D

M_CAP

Benign

0.0026

MetaRNN

Benign

0.16

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.29

PROVEAN

Uncertain

-4.0

D;D;D;D;D;D

Sift

Benign

0.033

D;D;T;T;T;T

Sift4G

Benign

0.11

T;T;T;T;T;T

Polyphen

1.0, 0.72

.;.;D;P;.;.

Vest4

0.24, 0.20, 0.24, 0.22

MutPred

0.61

.;Loss of methylation at R75 (P = 0.0188);Loss of methylation at R75 (P = 0.0188);Loss of methylation at R75 (P = 0.0188);.;.;

MVP

0.099

MPC

0.32

ClinPred

0.38

GERP RS

2.4

Varity_R

0.52

gMVP

0.27

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