rs2931761

Variant names:

• chr3-112471290-G-C
• rs2931761
• NM_181780.4:c.469C>G

Your query was ambiguous. Multiple possible variants found:

• chr3-112471290-G-C
• chr3-112471290-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_181780.4(BTLA):​c.469C>G​(p.Arg157Gly) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: BTLA NM_181780.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49
• Publications: 28 publications found

Genes affected

BTLA (HGNC:21087): (B and T lymphocyte associated) This gene encodes a member of the immunoglobulin superfamily. The encoded protein contains a single immunoglobulin (Ig) domain and is a receptor that relays inhibitory signals to suppress the immune response. Alternative splicing results in multiple transcript variants. Polymorphisms in this gene have been associated with an increased risk of rheumatoid arthritis. [provided by RefSeq, Aug 2011]

ENSG00000303317 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.052549243).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181780.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTLA	NM_181780.4	MANE Select	c.469C>G	p.Arg157Gly	missense	Exon 3 of 5	NP_861445.4	Q7Z6A9-1
	BTLA	NM_001085357.2		c.404-1486C>G		intron	N/A	NP_001078826.1	Q7Z6A9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTLA	ENST00000334529.10	TSL:1 MANE Select	c.469C>G	p.Arg157Gly	missense	Exon 3 of 5	ENSP00000333919.5	Q7Z6A9-1
	BTLA	ENST00000383680.5	TSL:1	c.404-1486C>G		intron	N/A	ENSP00000373178.4	Q7Z6A9-2
	BTLA	ENST00000858278.1		c.469C>G	p.Arg157Gly	missense	Exon 4 of 6	ENSP00000528337.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 52

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 183227

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.048
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.93
DANN	Benign	0.89
DEOGEN2	Benign	0.12	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0046	N
LIST_S2	Benign	0.11	T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.053	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-1.5
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.24	N
REVEL	Benign	0.023
Sift	Benign	0.070	T
Sift4G	Benign	0.16	T
Polyphen		0.0	B
Vest4		0.090
MutPred		0.38		Loss of glycosylation at P152 (P = 0.0228)
MVP		0.30
MPC		0.79
ClinPred		0.033	T
GERP RS		-4.9
Varity_R		0.067
gMVP		0.38
Mutation Taster		=100/0	polymorphism

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: rs2931761; hg19: chr3-112190137;