rs2281807

Positions:

• chr20-1629555-C-T

Variant summary

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

The NM_018556.4(SIRPG):​c.*84G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 152,250 control chromosomes in the GnomAD database, including 2,429 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 0.16 (2424 hom., cov: 31)
  • Exomes 𝑓: 0.22 (5 hom.)
• Consequence: SIRPG NM_018556.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.264

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIRPG	NM_018556.4	c.*84G>A		3_prime_UTR_variant	6/6	ENST00000303415.7	NP_061026.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIRPG	ENST00000303415.7	c.*84G>A		3_prime_UTR_variant	6/6	1	NM_018556.4	ENSP00000305529	P2

Frequencies

GnomAD3 genomes AF: 0.158 AC: 24009 AN: 151972 Hom.: 2418 Cov.: 31

Gnomad AFR AF: 0.0414

Gnomad AMI AF: 0.267

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.241

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.156

GnomAD4 exome AF: 0.219 AC: 35 AN: 160 Hom.: 5 Cov.: 0 AF XY: 0.206 AC XY: 21 AN XY: 102

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.167

Gnomad4 EAS exome AF: 0.750

Gnomad4 FIN exome AF: 0.200

Gnomad4 NFE exome AF: 0.217

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.158 AC: 24019 AN: 152090 Hom.: 2424 Cov.: 31 AF XY: 0.161 AC XY: 12004 AN XY: 74334

Gnomad4 AFR AF: 0.0413

Gnomad4 AMR AF: 0.278

Gnomad4 ASJ AF: 0.166

Gnomad4 EAS AF: 0.241

Gnomad4 SAS AF: 0.206

Gnomad4 FIN AF: 0.186

Gnomad4 NFE AF: 0.186

Gnomad4 OTH AF: 0.153

Alfa AF: 0.184 Hom.: 2843

Bravo AF: 0.160

Asia WGS AF: 0.198 AC: 687 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.63
DANN	Benign	0.63

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: rs2281807; hg19: chr20-1610201;