chr6-26383878-G-A

Variant names:

• chr6-26383878-G-A
• rs115247877
• NM_006995.5:c.57G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BS1 BS2

The NM_006995.5(BTN2A2):​c.57G>A​(p.Leu19Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0121 in 1,613,780 control chromosomes in the GnomAD database, including 159 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.010 (13 hom., cov: 31)
  • Exomes 𝑓: 0.012 (146 hom.)
• Consequence: BTN2A2 NM_006995.5 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.145

Genes affected

BTN2A2 (HGNC:1137): (butyrophilin subfamily 2 member A2) Butyrophilin is the major protein associated with fat droplets in the milk. This gene is a member of the BTN2 subfamily of genes, which encode proteins belonging to the butyrophilin protein family. The gene is located in a cluster on chromosome 6, consisting of seven genes belonging to the expanding B7/butyrophilin-like group, a subset of the immunoglobulin gene superfamily. The encoded protein is a type I receptor glycoprotein involved in lipid, fatty-acid and sterol metabolism. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2010]

ENSG00000291336 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 6-26383878-G-A is Benign according to our data. Variant chr6-26383878-G-A is described in ClinVar as [Benign]. Clinvar id is 3057121.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.145 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0101 (1531/152120) while in subpopulation AMR AF = 0.0193 (294/15272). AF 95% confidence interval is 0.0174. There are 13 homozygotes in GnomAd4. There are 734 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position FAILED quality control check.
• BS2: High Homozygotes in GnomAd4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTN2A2	NM_006995.5	c.57G>A	p.Leu19Leu	synonymous_variant	Exon 2 of 8	ENST00000356709.9	NP_008926.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BTN2A2	ENST00000356709.9	c.57G>A	p.Leu19Leu	synonymous_variant	Exon 2 of 8	1	NM_006995.5	ENSP00000349143.4

Frequencies

GnomAD3 genomes AF: 0.0101 AC: 1533 AN: 152002 Hom.: 14 Cov.: 31

Gnomad AFR AF: 0.00237

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0193

Gnomad ASJ AF: 0.0363

Gnomad EAS AF: 0.00232

Gnomad SAS AF: 0.0106

Gnomad FIN AF: 0.00226

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0131

Gnomad OTH AF: 0.0125

GnomAD2 exomes AF: 0.0114 AC: 2848 AN: 249958 AF XY: 0.0122

Gnomad AFR exome AF: 0.00179

Gnomad AMR exome AF: 0.0113

Gnomad ASJ exome AF: 0.0446

Gnomad EAS exome AF: 0.00109

Gnomad FIN exome AF: 0.00251

Gnomad NFE exome AF: 0.0126

Gnomad OTH exome AF: 0.0178

GnomAD4 exome AF: 0.0123 AC: 18026 AN: 1461660 Hom.: 146 Cov.: 31 AF XY: 0.0126 AC XY: 9177 AN XY: 727154

Gnomad4 AFR exome AF: 0.00197 AC: 66 AN: 33480

Gnomad4 AMR exome AF: 0.0130 AC: 580 AN: 44722

Gnomad4 ASJ exome AF: 0.0411 AC: 1074 AN: 26130

Gnomad4 EAS exome AF: 0.000428 AC: 17 AN: 39700

Gnomad4 SAS exome AF: 0.0139 AC: 1195 AN: 86252

Gnomad4 FIN exome AF: 0.00221 AC: 118 AN: 53408

Gnomad4 NFE exome AF: 0.0126 AC: 14005 AN: 1111806

Gnomad4 Remaining exome AF: 0.0141 AC: 851 AN: 60394

GnomAD4 genome AF: 0.0101 AC: 1531 AN: 152120 Hom.: 13 Cov.: 31 AF XY: 0.00987 AC XY: 734 AN XY: 74380

Gnomad4 AFR AF: 0.00239 AC: 0.00238669 AN: 0.00238669

Gnomad4 AMR AF: 0.0193 AC: 0.0192509 AN: 0.0192509

Gnomad4 ASJ AF: 0.0363 AC: 0.0362903 AN: 0.0362903

Gnomad4 EAS AF: 0.00232 AC: 0.00232108 AN: 0.00232108

Gnomad4 SAS AF: 0.0104 AC: 0.0103778 AN: 0.0103778

Gnomad4 FIN AF: 0.00226 AC: 0.00226458 AN: 0.00226458

Gnomad4 NFE AF: 0.0131 AC: 0.0131335 AN: 0.0131335

Gnomad4 OTH AF: 0.0123 AC: 0.0123223 AN: 0.0123223

Alfa AF: 0.00751 Hom.: 3

Bravo AF: 0.0115

Asia WGS AF: 0.00664 AC: 23 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

BTN2A2-related disorder Benign:1

Apr 29, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.5
DANN	Benign	0.82
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs115247877; hg19: chr6-26384106;