20-1937841-G-T

Variant names:

• chr20-1937841-G-T
• rs3197744
• NM_001040023.2:c.*273G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SIRPA	NM_001040023.2	c.*273G>T		3_prime_UTR_variant	Exon 8 of 8	ENST00000358771.5	NP_001035112.1

Ensembl

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

African (AFR) AF: 0.293 AC: 3186 AN: 10868

American (AMR) AF: 0.535 AC: 8025 AN: 15008

Ashkenazi Jewish (ASJ) AF: 0.590 AC: 6573 AN: 11136

East Asian (EAS) AF: 0.238 AC: 6119 AN: 25736

South Asian (SAS) AF: 0.407 AC: 12062 AN: 29658

European-Finnish (FIN) AF: 0.697 AC: 15417 AN: 22124

Middle Eastern (MID) AF: 0.526 AC: 820 AN: 1558

European-Non Finnish (NFE) AF: 0.615 AC: 125521 AN: 204102

Other (OTH) AF: 0.546 AC: 11311 AN: 20700

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

African (AFR) AF: 0.294 AC: 12169 AN: 41380

American (AMR) AF: 0.537 AC: 8200 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.570 AC: 1974 AN: 3466

East Asian (EAS) AF: 0.183 AC: 942 AN: 5148

South Asian (SAS) AF: 0.390 AC: 1880 AN: 4822

European-Finnish (FIN) AF: 0.703 AC: 7411 AN: 10542

Middle Eastern (MID) AF: 0.425 AC: 124 AN: 292

European-Non Finnish (NFE) AF: 0.620 AC: 42150 AN: 67934

Other (OTH) AF: 0.494 AC: 1041 AN: 2106

Alfa AF: 0.453 Hom.: 3892

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
PhyloP100		-0.66
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: rs3197744; hg19: chr20-1918487;