3-112466176-T-A

Variant names:

• chr3-112466176-T-A
• rs2082225158
• NM_181780.4:c.802A>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_181780.4(BTLA):​c.802A>T​(p.Asn268Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: BTLA NM_181780.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.52
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.802A>T	p.Asn268Tyr	missense	Exon 5 of 5	NP_861445.4	Q7Z6A9-1
	BTLA	NM_001085357.2		c.658A>T	p.Asn220Tyr	missense	Exon 4 of 4	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.802A>T	p.Asn268Tyr	missense	Exon 5 of 5	ENSP00000333919.5	Q7Z6A9-1
	BTLA	ENST00000383680.5	TSL:1	c.658A>T	p.Asn220Tyr	missense	Exon 4 of 4	ENSP00000373178.4	Q7Z6A9-2
	BTLA	ENST00000858278.1		c.802A>T	p.Asn268Tyr	missense	Exon 6 of 6	ENSP00000528337.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.53	D
Eigen	Benign	-0.014
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.0081	T
MetaRNN	Uncertain	0.55	D
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.5	L
PhyloP100		3.5
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.13
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.36
MutPred		0.37		Gain of catalytic residue at N268 (P = 0.0237)
MVP		0.76
MPC		1.8
ClinPred		0.97	D
GERP RS		3.9
Varity_R		0.069
gMVP		0.22
Mutation Taster		=91/9	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: rs2082225158; hg19: chr3-112185023;