rs2633562

Variant names:

• chr3-112477584-T-C
• rs2633562
• NM_181780.4:c.403+1871A>G

Variant summary

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

The NM_181780.4(BTLA):​c.403+1871A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 152,010 control chromosomes in the GnomAD database, including 3,646 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 0.15 (3646 hom., cov: 32)
• Consequence: BTLA NM_181780.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.499
• Publications: 8 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=-0.6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTLA	NM_181780.4	c.403+1871A>G		intron_variant	Intron 2 of 4	ENST00000334529.10	NP_861445.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BTLA	ENST00000334529.10	c.403+1871A>G		intron_variant	Intron 2 of 4	1	NM_181780.4	ENSP00000333919.5
BTLA	ENST00000383680.5	c.403+1871A>G		intron_variant	Intron 2 of 3	1		ENSP00000373178.4
ENSG00000303317	ENST00000793585.1	n.393-40424T>C		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22950 AN: 151892 Hom.: 3630 Cov.: 32

Gnomad AFR AF: 0.390

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.0467

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.0255

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0337

Gnomad OTH AF: 0.135

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.151 AC: 23010 AN: 152010 Hom.: 3646 Cov.: 32 AF XY: 0.151 AC XY: 11239 AN XY: 74304

African (AFR) AF: 0.391 AC: 16188 AN: 41418

American (AMR) AF: 0.146 AC: 2227 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0467 AC: 162 AN: 3466

East Asian (EAS) AF: 0.187 AC: 969 AN: 5174

South Asian (SAS) AF: 0.120 AC: 579 AN: 4826

European-Finnish (FIN) AF: 0.0255 AC: 270 AN: 10604

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0337 AC: 2287 AN: 67922

Other (OTH) AF: 0.134 AC: 282 AN: 2108

Alfa AF: 0.0748 Hom.: 4285

Bravo AF: 0.174

Asia WGS AF: 0.145 AC: 502 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	12
DANN	Benign	0.95
PhyloP100		0.50
Mutation Taster		=100/0	polymorphism (auto)

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: rs2633562; hg19: chr3-112196431;