rs1844089

Positions:

• chr3-112498887-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_181780.4(BTLA):​c.88+384C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 152,004 control chromosomes in the GnomAD database, including 8,073 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 0.24 (8073 hom., cov: 31)
• Consequence: BTLA NM_181780.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.304

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 (AFR) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BTLA	NM_181780.4	c.88+384C>T		intron_variant		ENST00000334529.10	NP_861445.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BTLA	ENST00000334529.10	c.88+384C>T		intron_variant		1	NM_181780.4	ENSP00000333919	P2
BTLA	ENST00000383680.4	c.88+384C>T		intron_variant		1		ENSP00000373178	A2

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36912 AN: 151884 Hom.: 8035 Cov.: 31

Gnomad AFR AF: 0.575

Gnomad AMI AF: 0.0462

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.0700

Gnomad MID AF: 0.175

Gnomad NFE AF: 0.0819

Gnomad OTH AF: 0.221

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

GnomAD4 genome AF: 0.243 AC: 37000 AN: 152004 Hom.: 8073 Cov.: 31 AF XY: 0.242 AC XY: 17961 AN XY: 74314

Gnomad4 AFR AF: 0.575

Gnomad4 AMR AF: 0.251

Gnomad4 ASJ AF: 0.103

Gnomad4 EAS AF: 0.245

Gnomad4 SAS AF: 0.178

Gnomad4 FIN AF: 0.0700

Gnomad4 NFE AF: 0.0818

Gnomad4 OTH AF: 0.218

Alfa AF: 0.176 Hom.: 613

Bravo AF: 0.277

Asia WGS AF: 0.218 AC: 756 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	0.44
DANN	Benign	0.69

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: rs1844089; hg19: chr3-112217734;