chr20-1618496-C-T

Variant names:

• chr20-1618496-C-T
• rs2209313
• NM_006065.5:c.76+1373G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006065.5(SIRPB1):​c.76+1373G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 152,168 control chromosomes in the GnomAD database, including 2,995 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.18 (2995 hom., cov: 32)
• Consequence: SIRPB1 NM_006065.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.06
• Publications: 20 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.06).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.305 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIRPB1	NM_006065.5	c.76+1373G>A		intron_variant	Intron 1 of 5	ENST00000381605.9	NP_006056.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIRPB1	ENST00000381605.9	c.76+1373G>A		intron_variant	Intron 1 of 5	1	NM_006065.5	ENSP00000371018.5
ENSG00000260861	ENST00000564763.1	c.76+1373G>A		intron_variant	Intron 1 of 2	4		ENSP00000457944.1

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27892 AN: 152050 Hom.: 2989 Cov.: 32

Gnomad AFR AF: 0.0803

Gnomad AMI AF: 0.251

Gnomad AMR AF: 0.312

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.201

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.198

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.183 AC: 27903 AN: 152168 Hom.: 2995 Cov.: 32 AF XY: 0.186 AC XY: 13851 AN XY: 74396

African (AFR) AF: 0.0801 AC: 3325 AN: 41510

American (AMR) AF: 0.313 AC: 4779 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 820 AN: 3468

East Asian (EAS) AF: 0.201 AC: 1040 AN: 5180

South Asian (SAS) AF: 0.185 AC: 891 AN: 4828

European-Finnish (FIN) AF: 0.185 AC: 1955 AN: 10590

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.212 AC: 14413 AN: 67984

Other (OTH) AF: 0.197 AC: 416 AN: 2114

Alfa AF: 0.188 Hom.: 1671

Bravo AF: 0.188

Asia WGS AF: 0.174 AC: 606 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.20
DANN	Benign	0.20
PhyloP100		-3.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2209313; hg19: chr20-1599142;