3-112484405-C-T

Variant names:

• chr3-112484405-C-T
• rs9288953
• NM_181780.4:c.89-4636G>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.89-4636G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 152,132 control chromosomes in the GnomAD database, including 7,413 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 0.28 (7413 hom., cov: 32)
• Consequence: BTLA NM_181780.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.03
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTLA	NM_181780.4	c.89-4636G>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.89-4636G>A		intron_variant	Intron 1 of 4	1	NM_181780.4	ENSP00000333919.5
BTLA	ENST00000383680.5	c.89-4636G>A		intron_variant	Intron 1 of 3	1		ENSP00000373178.4
ENSG00000303317	ENST00000793585.1	n.393-33603C>T		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42623 AN: 152014 Hom.: 7403 Cov.: 32

Gnomad AFR AF: 0.0713

Gnomad AMI AF: 0.417

Gnomad AMR AF: 0.297

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.530

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.470

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.268

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

GnomAD4 genome AF: 0.280 AC: 42632 AN: 152132 Hom.: 7413 Cov.: 32 AF XY: 0.287 AC XY: 21326 AN XY: 74368

African (AFR) AF: 0.0711 AC: 2953 AN: 41522

American (AMR) AF: 0.297 AC: 4548 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 990 AN: 3468

East Asian (EAS) AF: 0.530 AC: 2741 AN: 5176

South Asian (SAS) AF: 0.298 AC: 1437 AN: 4820

European-Finnish (FIN) AF: 0.470 AC: 4961 AN: 10564

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.353 AC: 23977 AN: 67968

Other (OTH) AF: 0.270 AC: 569 AN: 2110

Alfa AF: 0.320 Hom.: 2268

Bravo AF: 0.257

Asia WGS AF: 0.380 AC: 1320 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.12
DANN	Benign	0.76
PhyloP100		-2.0
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: rs9288953; hg19: chr3-112203252;