3-112463893-A-G

Variant names:

• chr3-112463893-A-G
• rs1982809
• ENST00000383680.5:c.*2215T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000383680.5(BTLA):​c.*2215T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 333,754 control chromosomes in the GnomAD database, including 16,836 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 0.29 (7474 hom., cov: 32)
  • Exomes 𝑓: 0.29 (9362 hom.)
• Consequence: BTLA ENST00000383680.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.449
• Publications: 27 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.733 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTLA	NM_181780.4	c.*2215T>C		downstream_gene_variant		ENST00000334529.10	NP_861445.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BTLA	ENST00000383680.5	c.*2215T>C		3_prime_UTR_variant	Exon 4 of 4	1		ENSP00000373178.4
ENSG00000303317	ENST00000793585.1	n.392+42984A>G		intron_variant	Intron 2 of 2
BTLA	ENST00000334529.10	c.*2215T>C		downstream_gene_variant		1	NM_181780.4	ENSP00000333919.5

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44432 AN: 151928 Hom.: 7453 Cov.: 32

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.753

Gnomad SAS AF: 0.387

Gnomad FIN AF: 0.298

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.294

GnomAD4 exome AF: 0.287 AC: 52087 AN: 181710 Hom.: 9362 AF XY: 0.284 AC XY: 26177 AN XY: 92118

African (AFR) AF: 0.273 AC: 1550 AN: 5672

American (AMR) AF: 0.419 AC: 2167 AN: 5176

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 1719 AN: 7072

East Asian (EAS) AF: 0.728 AC: 13024 AN: 17900

South Asian (SAS) AF: 0.362 AC: 582 AN: 1606

European-Finnish (FIN) AF: 0.263 AC: 3265 AN: 12418

Middle Eastern (MID) AF: 0.307 AC: 292 AN: 952

European-Non Finnish (NFE) AF: 0.219 AC: 25989 AN: 118630

Other (OTH) AF: 0.285 AC: 3499 AN: 12284

GnomAD4 genome AF: 0.293 AC: 44481 AN: 152044 Hom.: 7474 Cov.: 32 AF XY: 0.301 AC XY: 22363 AN XY: 74322

African (AFR) AF: 0.291 AC: 12076 AN: 41454

American (AMR) AF: 0.409 AC: 6246 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 867 AN: 3472

East Asian (EAS) AF: 0.753 AC: 3901 AN: 5180

South Asian (SAS) AF: 0.388 AC: 1865 AN: 4810

European-Finnish (FIN) AF: 0.298 AC: 3138 AN: 10546

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.227 AC: 15453 AN: 67982

Other (OTH) AF: 0.300 AC: 632 AN: 2110

Alfa AF: 0.252 Hom.: 22977

Bravo AF: 0.304

Asia WGS AF: 0.540 AC: 1874 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.72
DANN	Benign	0.29
PhyloP100		-0.45
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1982809; hg19: chr3-112182740;