20-1566235-C-G

Variant names:

• chr20-1566235-C-G
• NM_006065.5:c.1117G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006065.5(SIRPB1):​c.1117G>C​(p.Val373Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,458,702 control chromosomes in the GnomAD database, including 1 homozygotes. 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: 0.0000014 (1 hom.)
• Consequence: SIRPB1 NM_006065.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48

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]

ENSG00000260861 (HGNC:):

ACMG classification

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=0.06480515).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIRPB1	NM_006065.5	c.1117G>C	p.Val373Leu	missense_variant	Exon 5 of 6	ENST00000381605.9	NP_006056.2
SIRPB1	NM_001083910.4	c.466G>C	p.Val156Leu	missense_variant	Exon 3 of 4		NP_001077379.1
SIRPB1	NM_001330639.2	c.463G>C	p.Val155Leu	missense_variant	Exon 3 of 4		NP_001317568.1
SIRPB1	XM_005260641.4	c.1114G>C	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	c.1117G>C	p.Val373Leu	missense_variant	Exon 5 of 6	1	NM_006065.5	ENSP00000371018.5
ENSG00000260861	ENST00000564763.1	c.433+12103G>C		intron_variant	Intron 2 of 2	4		ENSP00000457944.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1458702 Hom.: 1 Cov.: 31 AF XY: 0.00000276 AC XY: 2 AN XY: 725288

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.010
DANN	Benign	0.79
DEOGEN2	Benign	0.018	T;.;.;.;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.23	T;T;T;T;T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.065	T;T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.1	L;.;.;.;.
PrimateAI	Benign	0.26	T
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		0.055	T
GERP RS		-0.40
Varity_R		0.054
gMVP		0.12

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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.

Other links and lift over

hg19: chr20-1546881;