Genetic Variant NM_006065.5:c.1117G>T (chr20-1566235-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006065.5(SIRPB1):c.1117G>T(p.Val373Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000891 in 1,458,702 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

SIRPB1
NM_006065.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.48

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:

ENSG00000260861 (HGNC:):

ENSG00000260861 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.052735984).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIRPB1	NM_006065.5 link	c.1117G>T	p.Val373Leu	missense_variant	Exon 5 of 6	ENST00000381605.9	NP_006056.2	O00241-1
SIRPB1	NM_001083910.4 link	c.466G>T	p.Val156Leu	missense_variant	Exon 3 of 4		NP_001077379.1	O00241-2
SIRPB1	NM_001330639.2 link	c.463G>T	p.Val155Leu	missense_variant	Exon 3 of 4		NP_001317568.1	O00241H9KV29
SIRPB1	XM_005260641.4 link	c.1114G>T	p.Val372Leu	missense_variant	Exon 5 of 6		XP_005260698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIRPB1	ENST00000381605.9 link	c.1117G>T	p.Val373Leu	missense_variant	Exon 5 of 6	1	NM_006065.5	ENSP00000371018.5		O00241-1
ENSG00000260861	ENST00000564763.1 link	c.433+12103G>T		intron_variant	Intron 2 of 2	4		ENSP00000457944.1		H3BV43

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000329

AC:

AN:

243346

Hom.:

AF XY:

0.0000152

AC XY:

AN XY:

131420

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000203

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000182

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000891

AC:

AN:

1458702

Hom.:

Cov.:

AF XY:

0.00000827

AC XY:

AN XY:

725288

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000105

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000494

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.66

CADD

Benign

0.0050

DANN

Benign

0.79

DEOGEN2

Benign

0.018

T;.;.;.;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.23

T;T;T;T;T

M_CAP

Benign

0.0027

MetaRNN

Benign

0.053

T;T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.1

L;.;.;.;.

PrimateAI

Benign

0.26

PROVEAN

Benign

-1.2

N;N;N;N;N

REVEL

Benign

0.011

Sift

Benign

0.075

T;T;T;D;T

Sift4G

Benign

0.30

T;T;T;T;T

Polyphen

0.0010

B;B;.;.;.

Vest4

0.086

MutPred

0.51

Loss of catalytic residue at V373 (P = 0.0682);.;.;.;.;

MVP

0.081

MPC

0.13

ClinPred

0.026

GERP RS

-0.40

Varity_R

0.054

gMVP

0.12

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.19

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over