Variant 7-100358854-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_178238.4(PILRB):c.229C>T(p.His77Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

PILRB
NM_178238.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.93

Variant links:

Genes affected

PILRB (HGNC:18297): (paired immunoglobin like type 2 receptor beta) The paired immunoglobin-like type 2 receptors consist of highly related activating and inhibitory receptors that are involved in the regulation of many aspects of the immune system. The paired immunoglobulin-like receptor genes are located in a tandem head-to-tail orientation on chromosome 7. This gene encodes the activating member of the receptor pair and contains a truncated cytoplasmic tail relative to its inhibitory counterpart (PILRA), that has a long cytoplasmic tail with immunoreceptor tyrosine-based inhibitory (ITIM) motifs. This gene is thought to have arisen from a duplication of the inhibitory PILRA gene and evolved to acquire its activating function. [provided by RefSeq, Jun 2013]

PILRB links:

STAG3L5P-PVRIG2P-PILRB (HGNC:):

STAG3L5P-PVRIG2P-PILRB links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.40271336).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PILRB	NM_178238.4 linkuse as main transcript	c.229C>T	p.His77Tyr	missense_variant	2/4	ENST00000609309.3
STAG3L5P-PVRIG2P-PILRB	NR_036570.1 linkuse as main transcript	n.2143-45C>T		intron_variant, non_coding_transcript_variant
PILRB	NM_001371931.2 linkuse as main transcript	c.229C>T	p.His77Tyr	missense_variant	2/5
STAG3L5P-PVRIG2P-PILRB	NR_036569.1 linkuse as main transcript	n.2774C>T		non_coding_transcript_exon_variant	16/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PILRB	ENST00000609309.3 linkuse as main transcript	c.229C>T	p.His77Tyr	missense_variant	2/4	1	NM_178238.4	P1	Q9UKJ0-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461892

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.68

D;.;.;.;.;.;T;D

Eigen

Benign

0.038

Eigen_PC

Benign

-0.15

FATHMM_MKL

Benign

0.39

M_CAP

Benign

0.0068

MetaRNN

Benign

0.40

T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.6

M;.;.;.;.;.;.;M

MutationTaster

Benign

1.0

D;D;N;N;N;N

PrimateAI

Benign

0.40

PROVEAN

Pathogenic

-5.7

D;D;D;D;D;.;D;.

REVEL

Benign

0.15

Sift

Uncertain

0.0020

D;D;D;D;D;.;D;.

Sift4G

Pathogenic

0.0

D;D;D;D;D;D;D;D

Polyphen

0.99

D;.;.;.;.;.;.;D

Vest4

0.38

MutPred

0.59

Loss of disorder (P = 0.0375);Loss of disorder (P = 0.0375);Loss of disorder (P = 0.0375);Loss of disorder (P = 0.0375);Loss of disorder (P = 0.0375);Loss of disorder (P = 0.0375);Loss of disorder (P = 0.0375);Loss of disorder (P = 0.0375);

MVP

0.11

ClinPred

0.99

GERP RS

2.5

Varity_R

0.57

gMVP

0.052

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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