7-100359372-A-G

Position:

• chr7-100359372-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_178238.4(PILRB):​c.490A>G​(p.Thr164Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PILRB NM_178238.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.533

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]

STAG3L5P-PVRIG2P-PILRB (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08543417).
• BP6: Variant 7-100359372-A-G is Benign according to our data. Variant chr7-100359372-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2308566.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PILRB	NM_178238.4	c.490A>G	p.Thr164Ala	missense_variant	3/4	ENST00000609309.3	NP_839956.1
PILRB	NM_001371931.2	c.490A>G	p.Thr164Ala	missense_variant	3/5		NP_001358860.1
STAG3L5P-PVRIG2P-PILRB	NR_036569.1	n.3035A>G		non_coding_transcript_exon_variant	17/18
STAG3L5P-PVRIG2P-PILRB	NR_036570.1	n.2359A>G		non_coding_transcript_exon_variant	16/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PILRB	ENST00000609309.3	c.490A>G	p.Thr164Ala	missense_variant	3/4	1	NM_178238.4	ENSP00000477365.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 17, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.092	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.43
DANN	Benign	0.14
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.055	N
LIST_S2	Benign	0.26	T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.085	T
MetaSVM	Benign	-1.0	T
PROVEAN	Pathogenic	-4.4	D
REVEL	Benign	0.16
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.38	T
Vest4		0.23
MVP		0.099
ClinPred		0.034	T
GERP RS		-1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-99956995;