6-26383832-C-T

Position:

• chr6-26383832-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_006995.5(BTN2A2):​c.11C>T​(p.Ala4Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00725 in 1,614,050 control chromosomes in the GnomAD database, including 90 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.012 (30 hom., cov: 32)
  • Exomes 𝑓: 0.0068 (60 hom.)
• Consequence: BTN2A2 NM_006995.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.566

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003088057).
• BP6: Variant 6-26383832-C-T is Benign according to our data. Variant chr6-26383832-C-T is described in ClinVar as [Benign]. Clinvar id is 790029.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0117 (1786/152226) while in subpopulation AFR AF= 0.027 (1119/41516). AF 95% confidence interval is 0.0256. There are 30 homozygotes in gnomad4. There are 845 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 30 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BTN2A2	NM_006995.5	c.11C>T	p.Ala4Val	missense_variant	2/8	ENST00000356709.9	NP_008926.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BTN2A2	ENST00000356709.9	c.11C>T	p.Ala4Val	missense_variant	2/8	1	NM_006995.5	ENSP00000349143	P1
	ENST00000707189.1	n.1000-169355C>T		intron_variant, non_coding_transcript_variant
	ENST00000707191.1	n.1001-148873C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0117 AC: 1776 AN: 152108 Hom.: 29 Cov.: 32

Gnomad AFR AF: 0.0268

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00995

Gnomad ASJ AF: 0.00950

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00104

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00629

Gnomad OTH AF: 0.0172

GnomAD3 exomes AF: 0.00669 AC: 1681 AN: 251442 Hom.: 17 AF XY: 0.00606 AC XY: 824 AN XY: 135900

Gnomad AFR exome AF: 0.0281

Gnomad AMR exome AF: 0.00882

Gnomad ASJ exome AF: 0.0136

Gnomad EAS exome AF: 0.000218

Gnomad SAS exome AF: 0.000490

Gnomad FIN exome AF: 0.00148

Gnomad NFE exome AF: 0.00589

Gnomad OTH exome AF: 0.0101

GnomAD4 exome AF: 0.00678 AC: 9913 AN: 1461824 Hom.: 60 Cov.: 30 AF XY: 0.00646 AC XY: 4700 AN XY: 727228

Gnomad4 AFR exome AF: 0.0287

Gnomad4 AMR exome AF: 0.0101

Gnomad4 ASJ exome AF: 0.0133

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.000556

Gnomad4 FIN exome AF: 0.00210

Gnomad4 NFE exome AF: 0.00670

Gnomad4 OTH exome AF: 0.00818

GnomAD4 genome AF: 0.0117 AC: 1786 AN: 152226 Hom.: 30 Cov.: 32 AF XY: 0.0113 AC XY: 845 AN XY: 74452

Gnomad4 AFR AF: 0.0270

Gnomad4 AMR AF: 0.00993

Gnomad4 ASJ AF: 0.00950

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.00104

Gnomad4 NFE AF: 0.00629

Gnomad4 OTH AF: 0.0170

Alfa AF: 0.00760 Hom.: 10

Bravo AF: 0.0141

TwinsUK AF: 0.00863 AC: 32

ALSPAC AF: 0.00675 AC: 26

ESP6500AA AF: 0.0250 AC: 110

ESP6500EA AF: 0.00802 AC: 69

ExAC AF: 0.00702 AC: 852

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 03, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.014	.;T;.;.;.;.;.;T;.;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.83	T;.;T;T;T;T;T;T;T;T
MetaRNN	Benign	0.0031	T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	0.63	N;N;N;.;.;N;N;N;.;.
MutationTaster	Benign	1.0	N;N;N;N;N;N
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.71	N;N;N;N;N;N;N;N;N;N
REVEL	Benign	0.052
Sift	Benign	0.13	T;T;D;T;D;D;D;T;T;D
Sift4G	Uncertain	0.012	D;D;D;D;D;D;D;D;D;D
Polyphen		0.034	B;B;.;.;.;.;.;B;.;.
Vest4		0.17
MVP		0.97
MPC		0.15
ClinPred		0.0044	T
GERP RS		1.1
Varity_R		0.039
gMVP		0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs73736234; hg19: chr6-26384060; COSMIC: COSV61858093;