rs9288953

chr3-112484405-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
BTLA	NM_181780.4	c.89-4636G>A		intron_variant		ENST00000334529.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BTLA	ENST00000334529.10	c.89-4636G>A		intron_variant		1	NM_181780.4	P2
BTLA	ENST00000383680.4	c.89-4636G>A		intron_variant		1		A2

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

Gnomad4 AFR AF: 0.0711

Gnomad4 AMR AF: 0.297

Gnomad4 ASJ AF: 0.285

Gnomad4 EAS AF: 0.530

Gnomad4 SAS AF: 0.298

Gnomad4 FIN AF: 0.470

Gnomad4 NFE AF: 0.353

Gnomad4 OTH AF: 0.270

Alfa AF: 0.322 Hom.: 1155

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs9288953; hg19: chr3-112203252;