6-26465997-A-C

Position:

• chr6-26465997-A-C

Variant summary

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

The NM_007049.5(BTN2A1):​c.955+24A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 1,613,956 control chromosomes in the GnomAD database, including 213,873 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 0.42 (15589 hom., cov: 33)
  • Exomes 𝑓: 0.51 (198284 hom.)
• Consequence: BTN2A1 NM_007049.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.213

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BTN2A1	NM_007049.5	c.955+24A>C		intron_variant		ENST00000312541.10	NP_008980.1
BTN2A1	NM_001197233.3	c.772+24A>C		intron_variant			NP_001184162.1
BTN2A1	NM_078476.4	c.955+24A>C		intron_variant			NP_510961.1
BTN2A1	NM_001197234.3	c.955+24A>C		intron_variant			NP_001184163.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BTN2A1	ENST00000312541.10	c.955+24A>C		intron_variant		1	NM_007049.5	ENSP00000312158.5

Frequencies

GnomAD3 genomes AF: 0.419 AC: 63661 AN: 152040 Hom.: 15581 Cov.: 33

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.441

Gnomad AMR AF: 0.514

Gnomad ASJ AF: 0.573

Gnomad EAS AF: 0.695

Gnomad SAS AF: 0.580

Gnomad FIN AF: 0.460

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.513

Gnomad OTH AF: 0.441

GnomAD3 exomes AF: 0.515 AC: 129569 AN: 251460 Hom.: 35264 AF XY: 0.520 AC XY: 70611 AN XY: 135896

Gnomad AFR exome AF: 0.137

Gnomad AMR exome AF: 0.572

Gnomad ASJ exome AF: 0.572

Gnomad EAS exome AF: 0.695

Gnomad SAS exome AF: 0.566

Gnomad FIN exome AF: 0.461

Gnomad NFE exome AF: 0.514

Gnomad OTH exome AF: 0.525

GnomAD4 exome AF: 0.515 AC: 752701 AN: 1461798 Hom.: 198284 Cov.: 60 AF XY: 0.516 AC XY: 375497 AN XY: 727196

Gnomad4 AFR exome AF: 0.128

Gnomad4 AMR exome AF: 0.563

Gnomad4 ASJ exome AF: 0.566

Gnomad4 EAS exome AF: 0.684

Gnomad4 SAS exome AF: 0.558

Gnomad4 FIN exome AF: 0.469

Gnomad4 NFE exome AF: 0.516

Gnomad4 OTH exome AF: 0.517

GnomAD4 genome AF: 0.418 AC: 63670 AN: 152158 Hom.: 15589 Cov.: 33 AF XY: 0.423 AC XY: 31453 AN XY: 74378

Gnomad4 AFR AF: 0.150

Gnomad4 AMR AF: 0.515

Gnomad4 ASJ AF: 0.573

Gnomad4 EAS AF: 0.695

Gnomad4 SAS AF: 0.579

Gnomad4 FIN AF: 0.460

Gnomad4 NFE AF: 0.513

Gnomad4 OTH AF: 0.446

Alfa AF: 0.505 Hom.: 19147

Bravo AF: 0.407

Asia WGS AF: 0.623 AC: 2164 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.53
DANN	Benign	0.30

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: rs1977198; hg19: chr6-26466225; COSMIC: COSV57004864; COSMIC: COSV57004864;