rs3746721

chr20-1630248-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_018556.4(SIRPG):c.1140C>T(p.Tyr380=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 1,569,130 control chromosomes in the GnomAD database, including 59,925 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 0.24 (5274 hom., cov: 31)
  • Exomes 𝑓: 0.26 (54651 hom.)
• Consequence: SIRPG NM_018556.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.70

Genes affected

SIRPG (HGNC:15757): (signal regulatory protein gamma) 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. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP7: Synonymous conserved (PhyloP=-1.7 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.588 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIRPG	NM_018556.4	c.1140C>T	p.Tyr380=	synonymous_variant	5/6	ENST00000303415.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIRPG	ENST00000303415.7	c.1140C>T	p.Tyr380=	synonymous_variant	5/6	1	NM_018556.4	P2

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36364 AN: 151846 Hom.: 5279 Cov.: 31

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.365

Gnomad EAS AF: 0.606

Gnomad SAS AF: 0.480

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.279

GnomAD3 exomes AF: 0.302 AC: 57237 AN: 189316 Hom.: 10125 AF XY: 0.313 AC XY: 31388 AN XY: 100364

Gnomad AFR exome AF: 0.110

Gnomad AMR exome AF: 0.293

Gnomad ASJ exome AF: 0.343

Gnomad EAS exome AF: 0.599

Gnomad SAS exome AF: 0.460

Gnomad FIN exome AF: 0.258

Gnomad NFE exome AF: 0.239

Gnomad OTH exome AF: 0.303

GnomAD4 exome AF: 0.263 AC: 372430 AN: 1417164 Hom.: 54651 Cov.: 32 AF XY: 0.270 AC XY: 189025 AN XY: 701004

Gnomad4 AFR exome AF: 0.112

Gnomad4 AMR exome AF: 0.289

Gnomad4 ASJ exome AF: 0.347

Gnomad4 EAS exome AF: 0.586

Gnomad4 SAS exome AF: 0.456

Gnomad4 FIN exome AF: 0.266

Gnomad4 NFE exome AF: 0.237

Gnomad4 OTH exome AF: 0.284

GnomAD4 genome AF: 0.239 AC: 36369 AN: 151966 Hom.: 5274 Cov.: 31 AF XY: 0.246 AC XY: 18306 AN XY: 74274

Gnomad4 AFR AF: 0.119

Gnomad4 AMR AF: 0.275

Gnomad4 ASJ AF: 0.365

Gnomad4 EAS AF: 0.606

Gnomad4 SAS AF: 0.477

Gnomad4 FIN AF: 0.256

Gnomad4 NFE AF: 0.250

Gnomad4 OTH AF: 0.281

Alfa AF: 0.261 Hom.: 12675

Bravo AF: 0.232

Asia WGS AF: 0.519 AC: 1804 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.71
Dann	Benign	0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs3746721; hg19: chr20-1610894; COSMIC: COSV53807023; COSMIC: COSV53807023;