NM_181780.4:c.88+9191G>A

Variant names:

• chr3-112490080-C-T
• rs2705535
• NM_181780.4:c.88+9191G>A

Variant summary

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

The NM_181780.4(BTLA):​c.88+9191G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0832 in 152,186 control chromosomes in the GnomAD database, including 1,096 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 0.083 (1096 hom., cov: 32)
• Consequence: BTLA NM_181780.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0730
• Publications: 13 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 (AFR) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTLA	NM_181780.4	c.88+9191G>A		intron_variant	Intron 1 of 4	ENST00000334529.10	NP_861445.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BTLA	ENST00000334529.10	c.88+9191G>A		intron_variant	Intron 1 of 4	1	NM_181780.4	ENSP00000333919.5
BTLA	ENST00000383680.5	c.88+9191G>A		intron_variant	Intron 1 of 3	1		ENSP00000373178.4
ENSG00000303317	ENST00000793585.1	n.393-27928C>T		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.0832 AC: 12650 AN: 152068 Hom.: 1096 Cov.: 32

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.0179

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.0412

Gnomad FIN AF: 0.0191

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0138

Gnomad OTH AF: 0.0707

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

GnomAD4 genome AF: 0.0832 AC: 12659 AN: 152186 Hom.: 1096 Cov.: 32 AF XY: 0.0840 AC XY: 6254 AN XY: 74412

African (AFR) AF: 0.204 AC: 8443 AN: 41484

American (AMR) AF: 0.111 AC: 1693 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0179 AC: 62 AN: 3470

East Asian (EAS) AF: 0.183 AC: 949 AN: 5180

South Asian (SAS) AF: 0.0413 AC: 199 AN: 4822

European-Finnish (FIN) AF: 0.0191 AC: 203 AN: 10606

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0138 AC: 941 AN: 68018

Other (OTH) AF: 0.0695 AC: 147 AN: 2114

Alfa AF: 0.0510 Hom.: 938

Bravo AF: 0.0988

Asia WGS AF: 0.105 AC: 364 AN: 3478

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	0.62
PhyloP100		-0.073
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: rs2705535; hg19: chr3-112208927;