Genetic Variant NM_006065.5:c.808G>T (chr20-1571081-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_006065.5(SIRPB1):c.808G>T(p.Val270Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,724 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 6.8e-7 ( 0 hom. )

Consequence

SIRPB1
NM_006065.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.63

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 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=0.25397807).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIRPB1	NM_006065.5 link	c.808G>T	p.Val270Phe	missense_variant	Exon 4 of 6	ENST00000381605.9	NP_006056.2	O00241-1
SIRPB1	XM_005260641.4 link	c.805G>T	p.Val269Phe	missense_variant	Exon 4 of 6		XP_005260698.1
SIRPB1	NM_001083910.4 link	c.434-4814G>T		intron_variant	Intron 2 of 3		NP_001077379.1	O00241-2
SIRPB1	NM_001330639.2 link	c.431-4814G>T		intron_variant	Intron 2 of 3		NP_001317568.1	O00241H9KV29

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIRPB1	ENST00000381605.9 link	c.808G>T	p.Val270Phe	missense_variant	Exon 4 of 6	1	NM_006065.5	ENSP00000371018.5		O00241-1
ENSG00000260861	ENST00000564763.1 link	c.433+7257G>T		intron_variant	Intron 2 of 2	4		ENSP00000457944.1		H3BV43

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461724

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727164

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

4.4

DANN

Benign

0.73

DEOGEN2

Benign

0.013

T;.

Eigen

Benign

-0.92

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.010

LIST_S2

Uncertain

0.87

D;D

M_CAP

Benign

0.00083

MetaRNN

Benign

0.25

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.8

M;.

PrimateAI

Benign

0.29

PROVEAN

Uncertain

-3.4

D;D

REVEL

Benign

0.17

Sift

Uncertain

0.0010

D;D

Sift4G

Benign

0.12

T;D

Polyphen

0.99

D;.

Vest4

0.38

MutPred

0.67

Loss of catalytic residue at V270 (P = 0.0526);.;

MVP

0.13

MPC

0.21

ClinPred

0.63

GERP RS

0.23

Varity_R

0.40

gMVP

0.55

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over