3-112471290-G-T

Variant names:

• chr3-112471290-G-T
• rs2931761
• NM_181780.4:c.469C>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.469C>A​(p.Arg157Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.998 in 1,614,114 control chromosomes in the GnomAD database, including 804,165 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 0.99 (74813 hom., cov: 31)
  • Exomes 𝑓: 1.0 (729352 hom.)
• Consequence: BTLA NM_181780.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49
• Publications: 28 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=7.1498323E-7).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181780.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTLA	NM_181780.4	MANE Select	c.469C>A	p.Arg157Ser	missense	Exon 3 of 5	NP_861445.4	Q7Z6A9-1
	BTLA	NM_001085357.2		c.404-1486C>A		intron	N/A	NP_001078826.1	Q7Z6A9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTLA	ENST00000334529.10	TSL:1 MANE Select	c.469C>A	p.Arg157Ser	missense	Exon 3 of 5	ENSP00000333919.5	Q7Z6A9-1
	BTLA	ENST00000383680.5	TSL:1	c.404-1486C>A		intron	N/A	ENSP00000373178.4	Q7Z6A9-2
	BTLA	ENST00000858278.1		c.469C>A	p.Arg157Ser	missense	Exon 4 of 6	ENSP00000528337.1

Frequencies

GnomAD3 genomes AF: 0.991 AC: 150825 AN: 152164 Hom.: 74759 Cov.: 31

Gnomad AFR AF: 0.970

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.997

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 0.995

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.997

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.992

GnomAD2 exomes AF: 0.997 AC: 250749 AN: 251438 AF XY: 0.998

Gnomad AFR exome AF: 0.968

Gnomad AMR exome AF: 0.999

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 0.994

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 1.00

Gnomad OTH exome AF: 0.999

GnomAD4 exome AF: 0.999 AC: 1460239 AN: 1461832 Hom.: 729352 Cov.: 52 AF XY: 0.999 AC XY: 726514 AN XY: 727220

African (AFR) AF: 0.967 AC: 32372 AN: 33472

American (AMR) AF: 0.999 AC: 44661 AN: 44724

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 26134 AN: 26134

East Asian (EAS) AF: 0.995 AC: 39496 AN: 39696

South Asian (SAS) AF: 0.999 AC: 86201 AN: 86254

European-Finnish (FIN) AF: 1.00 AC: 53420 AN: 53420

Middle Eastern (MID) AF: 0.997 AC: 5751 AN: 5768

European-Non Finnish (NFE) AF: 1.00 AC: 1111958 AN: 1111970

Other (OTH) AF: 0.998 AC: 60246 AN: 60394

GnomAD4 genome AF: 0.991 AC: 150938 AN: 152282 Hom.: 74813 Cov.: 31 AF XY: 0.992 AC XY: 73851 AN XY: 74454

African (AFR) AF: 0.970 AC: 40292 AN: 41542

American (AMR) AF: 0.997 AC: 15262 AN: 15304

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 0.995 AC: 5154 AN: 5180

South Asian (SAS) AF: 0.999 AC: 4814 AN: 4820

European-Finnish (FIN) AF: 1.00 AC: 10612 AN: 10612

Middle Eastern (MID) AF: 0.997 AC: 293 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68029 AN: 68032

Other (OTH) AF: 0.992 AC: 2098 AN: 2114

Alfa AF: 0.997 Hom.: 183227

Bravo AF: 0.990

TwinsUK AF: 1.00 AC: 3708

ALSPAC AF: 1.00 AC: 3854

ESP6500AA AF: 0.972 AC: 4284

ESP6500EA AF: 1.00 AC: 8600

ExAC AF: 0.997 AC: 121035

Asia WGS AF: 0.991 AC: 3446 AN: 3478

EpiCase AF: 1.00

EpiControl AF: 1.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.14
DANN	Benign	0.38
DEOGEN2	Benign	0.093	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0013	N
LIST_S2	Benign	0.068	T
MetaRNN	Benign	7.1e-7	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.4	N
PhyloP100		-1.5
PrimateAI	Benign	0.22	T
PROVEAN	Benign	1.3	N
REVEL	Benign	0.033
Sift	Benign	1.0	T
Sift4G	Benign	0.84	T
Polyphen		0.0	B
Vest4		0.045
MPC		0.69
ClinPred		0.010	T
GERP RS		-4.9
Varity_R		0.10
gMVP		0.34
Mutation Taster		=99/1	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: rs2931761; hg19: chr3-112190137; COSMIC: COSV107400910; COSMIC: COSV107400910;