rs9288952

Variant names:

• chr3-112466178-G-A
• rs9288952
• NM_181780.4:c.800C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-112466178-G-A
• chr3-112466178-G-C

Variant summary

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

The NM_181780.4(BTLA):​c.800C>T​(p.Pro267Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.9 in 1,612,738 control chromosomes in the GnomAD database, including 674,193 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.74 (48080 hom., cov: 32)
  • Exomes 𝑓: 0.92 (626113 hom.)
• Consequence: BTLA NM_181780.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.104
• Publications: 50 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 (MetaRNN=7.8478456E-7).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.952 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTLA	NM_181780.4	c.800C>T	p.Pro267Leu	missense_variant	Exon 5 of 5	ENST00000334529.10	NP_861445.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BTLA	ENST00000334529.10	c.800C>T	p.Pro267Leu	missense_variant	Exon 5 of 5	1	NM_181780.4	ENSP00000333919.5
BTLA	ENST00000383680.5	c.656C>T	p.Pro219Leu	missense_variant	Exon 4 of 4	1		ENSP00000373178.4
BTLA	ENST00000474965.1	n.304C>T		non_coding_transcript_exon_variant	Exon 3 of 3	2
ENSG00000303317	ENST00000793585.1	n.392+45269G>A		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.738 AC: 112243 AN: 151996 Hom.: 48076 Cov.: 32

Gnomad AFR AF: 0.277

Gnomad AMI AF: 0.961

Gnomad AMR AF: 0.761

Gnomad ASJ AF: 0.928

Gnomad EAS AF: 0.727

Gnomad SAS AF: 0.815

Gnomad FIN AF: 0.971

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.958

Gnomad OTH AF: 0.782

GnomAD2 exomes AF: 0.836 AC: 209705 AN: 250910 AF XY: 0.855

Gnomad AFR exome AF: 0.265

Gnomad AMR exome AF: 0.659

Gnomad ASJ exome AF: 0.928

Gnomad EAS exome AF: 0.722

Gnomad FIN exome AF: 0.967

Gnomad NFE exome AF: 0.956

Gnomad OTH exome AF: 0.882

GnomAD4 exome AF: 0.917 AC: 1339490 AN: 1460624 Hom.: 626113 Cov.: 52 AF XY: 0.917 AC XY: 666434 AN XY: 726416

African (AFR) AF: 0.247 AC: 8253 AN: 33468

American (AMR) AF: 0.673 AC: 30044 AN: 44650

Ashkenazi Jewish (ASJ) AF: 0.929 AC: 24282 AN: 26128

East Asian (EAS) AF: 0.728 AC: 28868 AN: 39638

South Asian (SAS) AF: 0.826 AC: 71050 AN: 86044

European-Finnish (FIN) AF: 0.967 AC: 51632 AN: 53410

Middle Eastern (MID) AF: 0.858 AC: 4941 AN: 5758

European-Non Finnish (NFE) AF: 0.961 AC: 1067422 AN: 1111190

Other (OTH) AF: 0.878 AC: 52998 AN: 60338

GnomAD4 genome AF: 0.738 AC: 112249 AN: 152114 Hom.: 48080 Cov.: 32 AF XY: 0.741 AC XY: 55164 AN XY: 74398

African (AFR) AF: 0.276 AC: 11442 AN: 41408

American (AMR) AF: 0.761 AC: 11628 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.928 AC: 3222 AN: 3472

East Asian (EAS) AF: 0.726 AC: 3756 AN: 5170

South Asian (SAS) AF: 0.816 AC: 3937 AN: 4824

European-Finnish (FIN) AF: 0.971 AC: 10317 AN: 10620

Middle Eastern (MID) AF: 0.854 AC: 251 AN: 294

European-Non Finnish (NFE) AF: 0.958 AC: 65164 AN: 68020

Other (OTH) AF: 0.783 AC: 1656 AN: 2114

Alfa AF: 0.874 Hom.: 209001

Bravo AF: 0.698

TwinsUK AF: 0.965 AC: 3577

ALSPAC AF: 0.971 AC: 3743

ESP6500AA AF: 0.296 AC: 1302

ESP6500EA AF: 0.958 AC: 8240

ExAC AF: 0.833 AC: 101127

Asia WGS AF: 0.756 AC: 2630 AN: 3478

EpiCase AF: 0.954

EpiControl AF: 0.951

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.4
DANN	Benign	0.25
DEOGEN2	Benign	0.083	T;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0027	N
LIST_S2	Benign	0.30	T;T
MetaRNN	Benign	7.8e-7	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;.
PhyloP100		0.10
PrimateAI	Benign	0.24	T
PROVEAN	Benign	1.6	N;N
REVEL	Benign	0.0090
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;B
Vest4		0.010
MPC		0.63
ClinPred		0.0000096	T
GERP RS		-0.71
Varity_R		0.019
gMVP		0.17
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: rs9288952; hg19: chr3-112185025; COSMIC: COSV57939708; COSMIC: COSV57939708;