chr3-112469774-C-T

Variant names:

• chr3-112469774-C-T
• rs1484088538
• NM_181780.4:c.578G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_181780.4(BTLA):​c.578G>A​(p.Gly193Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,194 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: BTLA NM_181780.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.518
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24455494).

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.578G>A	p.Gly193Glu	missense	Exon 4 of 5	NP_861445.4	Q7Z6A9-1
	BTLA	NM_001085357.2		c.434G>A	p.Gly145Glu	missense	Exon 3 of 4	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.578G>A	p.Gly193Glu	missense	Exon 4 of 5	ENSP00000333919.5	Q7Z6A9-1
	BTLA	ENST00000383680.5	TSL:1	c.434G>A	p.Gly145Glu	missense	Exon 3 of 4	ENSP00000373178.4	Q7Z6A9-2
	BTLA	ENST00000858278.1		c.578G>A	p.Gly193Glu	missense	Exon 5 of 6	ENSP00000528337.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000400 AC: 1 AN: 249744 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459194 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726036

African (AFR) AF: 0.00 AC: 0 AN: 33438

American (AMR) AF: 0.0000224 AC: 1 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26106

East Asian (EAS) AF: 0.00 AC: 0 AN: 39650

South Asian (SAS) AF: 0.00 AC: 0 AN: 86204

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51668

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111342

Other (OTH) AF: 0.00 AC: 0 AN: 60322

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	7.2
DANN	Benign	0.66
DEOGEN2	Uncertain	0.43	T
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.063	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		0.52
PrimateAI	Benign	0.26	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.068
Sift	Benign	0.078	T
Sift4G	Uncertain	0.013	D
Polyphen		0.67	P
Vest4		0.078
MutPred		0.70		Loss of loop (P = 0.0288)
MVP		0.56
MPC		0.82
ClinPred		0.042	T
GERP RS		-1.1
Varity_R		0.11
gMVP		0.38
Mutation Taster		=92/8	polymorphism

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: rs1484088538; hg19: chr3-112188621;