rs7792525

Variant names:

• chr7-100374499-A-G
• rs7792525
• NM_013439.3:c.454+66A>G

Variant summary

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

The NM_013439.3(PILRA):​c.454+66A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 1,582,388 control chromosomes in the GnomAD database, including 25,525 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 (2114 hom., cov: 30)
  • Exomes 𝑓: 0.18 (23411 hom.)
• Consequence: PILRA NM_013439.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.845
• Publications: 22 publications found

Genes affected

PILRA (HGNC:20396): (paired immunoglobin like type 2 receptor alpha) Cell signaling pathways rely on a dynamic interaction between activating and inhibiting processes. SHP-1-mediated dephosphorylation of protein tyrosine residues is central to the regulation of several cell signaling pathways. Two types of inhibitory receptor superfamily members are immunoreceptor tyrosine-based inhibitory motif (ITIM)-bearing receptors and their non-ITIM-bearing, activating counterparts. Control of cell signaling via SHP-1 is thought to occur through a balance between PILRalpha-mediated inhibition and PILRbeta-mediated activation. These paired immunoglobulin-like receptor genes are located in a tandem head-to-tail orientation on chromosome 7. This particular gene encodes the ITIM-bearing member of the receptor pair, which functions in the inhibitory role. Alternative splicing has been observed at this locus and three variants, each encoding a distinct isoform, are described. [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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PILRA	NM_013439.3	c.454+66A>G		intron_variant	Intron 2 of 6	ENST00000198536.7	NP_038467.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PILRA	ENST00000198536.7	c.454+66A>G		intron_variant	Intron 2 of 6	1	NM_013439.3	ENSP00000198536.2

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24204 AN: 151758 Hom.: 2103 Cov.: 30

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.307

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.0335

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.188

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.168

GnomAD2 exomes AF: 0.150 AC: 36174 AN: 240738 AF XY: 0.154

Gnomad AFR exome AF: 0.122

Gnomad AMR exome AF: 0.0847

Gnomad ASJ exome AF: 0.221

Gnomad EAS exome AF: 0.0335

Gnomad FIN exome AF: 0.217

Gnomad NFE exome AF: 0.184

Gnomad OTH exome AF: 0.173

GnomAD4 exome AF: 0.178 AC: 254069 AN: 1430512 Hom.: 23411 Cov.: 27 AF XY: 0.178 AC XY: 126997 AN XY: 713250

African (AFR) AF: 0.121 AC: 4003 AN: 32996

American (AMR) AF: 0.0892 AC: 3975 AN: 44570

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 5670 AN: 25964

East Asian (EAS) AF: 0.0333 AC: 1315 AN: 39534

South Asian (SAS) AF: 0.126 AC: 10756 AN: 85464

European-Finnish (FIN) AF: 0.216 AC: 10300 AN: 47728

Middle Eastern (MID) AF: 0.215 AC: 1234 AN: 5730

European-Non Finnish (NFE) AF: 0.190 AC: 206556 AN: 1088992

Other (OTH) AF: 0.172 AC: 10260 AN: 59534

GnomAD4 genome AF: 0.160 AC: 24236 AN: 151876 Hom.: 2114 Cov.: 30 AF XY: 0.159 AC XY: 11829 AN XY: 74214

African (AFR) AF: 0.123 AC: 5105 AN: 41394

American (AMR) AF: 0.120 AC: 1824 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.225 AC: 780 AN: 3462

East Asian (EAS) AF: 0.0333 AC: 172 AN: 5158

South Asian (SAS) AF: 0.119 AC: 573 AN: 4814

European-Finnish (FIN) AF: 0.220 AC: 2322 AN: 10560

Middle Eastern (MID) AF: 0.185 AC: 54 AN: 292

European-Non Finnish (NFE) AF: 0.188 AC: 12775 AN: 67922

Other (OTH) AF: 0.167 AC: 352 AN: 2106

Alfa AF: 0.177 Hom.: 1996

Bravo AF: 0.152

Asia WGS AF: 0.0820 AC: 287 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.1
DANN	Benign	0.36
PhyloP100		-0.84
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: rs7792525; hg19: chr7-99972122; COSMIC: COSV52199263;