6-26463346-G-T

Variant names:

• chr6-26463346-G-T
• rs13195401
• NM_007049.5:c.533G>T

Variant summary

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

The NM_007049.5(BTN2A1):​c.533G>T​(p.Trp178Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0787 in 1,613,746 control chromosomes in the GnomAD database, including 6,473 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 0.051 (271 hom., cov: 31)
  • Exomes 𝑓: 0.082 (6202 hom.)
• Consequence: BTN2A1 NM_007049.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.21
• Publications: 30 publications found

Genes affected

BTN2A1 (HGNC:1136): (butyrophilin subfamily 2 member A1) This gene encodes a member of the immunoglobulin superfamily. The gene is located in a cluster of butyrophilin-like genes in the juxta-telomeric region of the major histocompatibility complex on chromosome 6. A pseudogene of this gene has been identified in this cluster. The encoded protein is an integral plasma membrane protein involved in lipid, fatty-acid, and sterol metabolism. Alterations in this gene may be associated with several disease states including metabolic syndrome. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2013]

ENSG00000291336 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004269719).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0802 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007049.5. 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
	BTN2A1	NM_007049.5	MANE Select	c.533G>T	p.Trp178Leu	missense	Exon 4 of 8	NP_008980.1	Q7KYR7-2
	BTN2A1	NM_001197233.3		c.350G>T	p.Trp117Leu	missense	Exon 3 of 7	NP_001184162.1	Q7KYR7-5
	BTN2A1	NM_078476.4		c.533G>T	p.Trp178Leu	missense	Exon 4 of 8	NP_510961.1	Q7KYR7-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTN2A1	ENST00000312541.10	TSL:1 MANE Select	c.533G>T	p.Trp178Leu	missense	Exon 4 of 8	ENSP00000312158.5	Q7KYR7-2
	BTN2A1	ENST00000429381.5	TSL:1	c.533G>T	p.Trp178Leu	missense	Exon 4 of 8	ENSP00000416945.1	Q7KYR7-4
	BTN2A1	ENST00000469185.5	TSL:1	c.533G>T	p.Trp178Leu	missense	Exon 4 of 8	ENSP00000419043.1	Q7KYR7-6

Frequencies

GnomAD3 genomes AF: 0.0515 AC: 7820 AN: 151970 Hom.: 271 Cov.: 31

Gnomad AFR AF: 0.0291

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.0249

Gnomad ASJ AF: 0.0199

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0388

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0821

Gnomad OTH AF: 0.0354

GnomAD2 exomes AF: 0.0452 AC: 11355 AN: 251344 AF XY: 0.0448

Gnomad AFR exome AF: 0.0300

Gnomad AMR exome AF: 0.0172

Gnomad ASJ exome AF: 0.0189

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0400

Gnomad NFE exome AF: 0.0788

Gnomad OTH exome AF: 0.0419

GnomAD4 exome AF: 0.0816 AC: 119215 AN: 1461658 Hom.: 6202 Cov.: 31 AF XY: 0.0783 AC XY: 56899 AN XY: 727126

African (AFR) AF: 0.0283 AC: 947 AN: 33478

American (AMR) AF: 0.0176 AC: 785 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.0200 AC: 523 AN: 26130

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39700

South Asian (SAS) AF: 0.000151 AC: 13 AN: 86258

European-Finnish (FIN) AF: 0.0400 AC: 2135 AN: 53408

Middle Eastern (MID) AF: 0.00433 AC: 25 AN: 5768

European-Non Finnish (NFE) AF: 0.0997 AC: 110826 AN: 1111814

Other (OTH) AF: 0.0655 AC: 3957 AN: 60384

GnomAD4 genome AF: 0.0514 AC: 7818 AN: 152088 Hom.: 271 Cov.: 31 AF XY: 0.0467 AC XY: 3475 AN XY: 74346

African (AFR) AF: 0.0290 AC: 1204 AN: 41494

American (AMR) AF: 0.0249 AC: 380 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0199 AC: 69 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5150

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4816

European-Finnish (FIN) AF: 0.0388 AC: 411 AN: 10596

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0820 AC: 5576 AN: 67966

Other (OTH) AF: 0.0351 AC: 74 AN: 2110

Alfa AF: 0.0640 Hom.: 291

Bravo AF: 0.0500

TwinsUK AF: 0.119 AC: 442

ALSPAC AF: 0.106 AC: 410

ESP6500AA AF: 0.0311 AC: 137

ESP6500EA AF: 0.0801 AC: 689

ExAC AF: 0.0463 AC: 5619

Asia WGS AF: 0.00549 AC: 20 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.60
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	26
DANN	Uncertain	0.98
DEOGEN2	Benign	0.12	T
Eigen	Uncertain	0.36
Eigen_PC	Benign	0.096
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.94	D
MetaRNN	Benign	0.0043	T
MetaSVM	Uncertain	-0.23	T
MutationAssessor	Pathogenic	4.1	H
PhyloP100		4.2
PrimateAI	Benign	0.48	T
PROVEAN	Pathogenic	-11	D
REVEL	Benign	0.17
Sift	Uncertain	0.0030	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.36
MPC		0.54
ClinPred		0.12	T
GERP RS		2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.81
gMVP		0.75
Mutation Taster		=97/3	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: rs13195401; hg19: chr6-26463574; COSMIC: COSV107356287; COSMIC: COSV107356287;