Genetic Variant NM_013439.3:c.454+66A>G (chr7-100374499-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.845

Variant links:

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]

PILRA links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 link	c.454+66A>G		intron_variant	Intron 2 of 6	ENST00000198536.7	NP_038467.2	Q9UKJ1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PILRA	ENST00000198536.7 link	c.454+66A>G		intron_variant	Intron 2 of 6	1	NM_013439.3	ENSP00000198536.2		Q9UKJ1-1

Frequencies

GnomAD3 genomes

AF:

0.159

AC:

24204

AN:

151758

Hom.:

2103

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.150

AC:

36174

AN:

240738

Hom.:

3043

AF XY:

0.154

AC XY:

20146

AN XY:

131098

show subpopulations

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 SAS exome

AF:

0.123

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.:

AF XY:

0.178

AC XY:

126997

AN XY:

713250

show subpopulations

Gnomad4 AFR exome

AF:

0.121

Gnomad4 AMR exome

AF:

0.0892

Gnomad4 ASJ exome

AF:

0.218

Gnomad4 EAS exome

AF:

0.0333

Gnomad4 SAS exome

AF:

0.126

Gnomad4 FIN exome

AF:

0.216

Gnomad4 NFE exome

AF:

0.190

Gnomad4 OTH exome

AF:

0.172

GnomAD4 genome

AF:

0.160

AC:

24236

AN:

151876

Hom.:

2114

Cov.:

AF XY:

0.159

AC XY:

11829

AN XY:

74214

show subpopulations

Gnomad4 AFR

AF:

0.123

Gnomad4 AMR

AF:

0.120

Gnomad4 ASJ

AF:

0.225

Gnomad4 EAS

AF:

0.0333

Gnomad4 SAS

AF:

0.119

Gnomad4 FIN

AF:

0.220

Gnomad4 NFE

AF:

0.188

Gnomad4 OTH

AF:

0.167

Alfa

AF:

0.183

Hom.:

1863

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over