6-26465997-A-C

Variant names:

• chr6-26465997-A-C
• rs1977198
• NM_007049.5:c.955+24A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 25 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 (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 rank	MANE	Protein	UniProt
BTN2A1	NM_007049.5	c.955+24A>C		intron_variant	Intron 6 of 7	ENST00000312541.10	NP_008980.1
BTN2A1	NM_001197233.3	c.772+24A>C		intron_variant	Intron 5 of 6		NP_001184162.1
BTN2A1	NM_078476.4	c.955+24A>C		intron_variant	Intron 6 of 7		NP_510961.1
BTN2A1	NM_001197234.3	c.955+24A>C		intron_variant	Intron 6 of 7		NP_001184163.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BTN2A1	ENST00000312541.10	c.955+24A>C		intron_variant	Intron 6 of 7	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

GnomAD2 exomes AF: 0.515 AC: 129569 AN: 251460 AF XY: 0.520

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 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

African (AFR) AF: 0.128 AC: 4281 AN: 33476

American (AMR) AF: 0.563 AC: 25195 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.566 AC: 14780 AN: 26136

East Asian (EAS) AF: 0.684 AC: 27138 AN: 39700

South Asian (SAS) AF: 0.558 AC: 48098 AN: 86256

European-Finnish (FIN) AF: 0.469 AC: 25045 AN: 53420

Middle Eastern (MID) AF: 0.494 AC: 2844 AN: 5760

European-Non Finnish (NFE) AF: 0.516 AC: 574120 AN: 1111930

Other (OTH) AF: 0.517 AC: 31200 AN: 60396

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

African (AFR) AF: 0.150 AC: 6214 AN: 41528

American (AMR) AF: 0.515 AC: 7871 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.573 AC: 1988 AN: 3468

East Asian (EAS) AF: 0.695 AC: 3591 AN: 5168

South Asian (SAS) AF: 0.579 AC: 2797 AN: 4832

European-Finnish (FIN) AF: 0.460 AC: 4871 AN: 10586

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.513 AC: 34860 AN: 67976

Other (OTH) AF: 0.446 AC: 942 AN: 2112

Alfa AF: 0.491 Hom.: 24274

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
PhyloP100		-0.21
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: rs1977198; hg19: chr6-26466225; COSMIC: COSV57004864; COSMIC: COSV57004864;