rs3197744

Positions:

• chr20-1937841-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001040023.2(SIRPA):​c.*273G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.538 in 492,748 control chromosomes in the GnomAD database, including 76,569 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 0.50 (21134 hom., cov: 30)
  • Exomes 𝑓: 0.55 (55435 hom.)
• Consequence: SIRPA NM_001040023.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.661

Genes affected

SIRPA (HGNC:9662): (signal regulatory protein alpha) 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 can be phosphorylated by tyrosine kinases. The phospho-tyrosine residues of this PTP have been shown to recruit SH2 domain containing tyrosine phosphatases (PTP), and serve as substrates of PTPs. This protein was found to participate in signal transduction mediated by various growth factor receptors. CD47 has been demonstrated to be a ligand for this receptor protein. This gene and its product share very high similarity with several other members of the SIRP family. These related genes are located in close proximity to each other on chromosome 20p13. Multiple alternatively spliced transcript variants have been determined for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.615 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIRPA	NM_001040023.2	c.*273G>T		3_prime_UTR_variant	8/8	ENST00000358771.5	NP_001035112.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIRPA	ENST00000358771.5	c.*273G>T		3_prime_UTR_variant	8/8	1	NM_001040023.2	ENSP00000351621.4
SIRPA	ENST00000356025.7	c.*273G>T		3_prime_UTR_variant	9/9	1		ENSP00000348307.3
SIRPA	ENST00000400068.7	c.*273G>T		3_prime_UTR_variant	9/9	1		ENSP00000382941.4
SIRPA	ENST00000622179.4	c.*273G>T		3_prime_UTR_variant	9/9	5		ENSP00000478763.1

Frequencies

GnomAD3 genomes AF: 0.503 AC: 76257 AN: 151740 Hom.: 21137 Cov.: 30

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.538

Gnomad ASJ AF: 0.570

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.390

Gnomad FIN AF: 0.703

Gnomad MID AF: 0.433

Gnomad NFE AF: 0.620

Gnomad OTH AF: 0.500

GnomAD4 exome AF: 0.555 AC: 189034 AN: 340890 Hom.: 55435 Cov.: 3 AF XY: 0.548 AC XY: 96415 AN XY: 175960

Gnomad4 AFR exome AF: 0.293

Gnomad4 AMR exome AF: 0.535

Gnomad4 ASJ exome AF: 0.590

Gnomad4 EAS exome AF: 0.238

Gnomad4 SAS exome AF: 0.407

Gnomad4 FIN exome AF: 0.697

Gnomad4 NFE exome AF: 0.615

Gnomad4 OTH exome AF: 0.546

GnomAD4 genome AF: 0.502 AC: 76253 AN: 151858 Hom.: 21134 Cov.: 30 AF XY: 0.501 AC XY: 37204 AN XY: 74194

Gnomad4 AFR AF: 0.294

Gnomad4 AMR AF: 0.537

Gnomad4 ASJ AF: 0.570

Gnomad4 EAS AF: 0.183

Gnomad4 SAS AF: 0.390

Gnomad4 FIN AF: 0.703

Gnomad4 NFE AF: 0.620

Gnomad4 OTH AF: 0.494

Alfa AF: 0.557 Hom.: 3231

Bravo AF: 0.480

Asia WGS AF: 0.259 AC: 900 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.73
DANN	Benign	0.83

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

Other links and lift over

dbSNP: rs3197744; hg19: chr20-1918487;