chr6-26463370-C-T

Variant names:

• chr6-26463370-C-T
• rs139773763
• NM_007049.5:c.557C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_007049.5(BTN2A1):​c.557C>T​(p.Ala186Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000062 in 1,613,936 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00025 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000042 (0 hom.)
• Consequence: BTN2A1 NM_007049.5 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.746
• Publications: 0 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=0.007840812).
• BP6: Variant 6-26463370-C-T is Benign according to our data. Variant chr6-26463370-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2342805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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.557C>T	p.Ala186Val	missense	Exon 4 of 8	NP_008980.1	Q7KYR7-2
	BTN2A1	NM_001197233.3		c.374C>T	p.Ala125Val	missense	Exon 3 of 7	NP_001184162.1	Q7KYR7-5
	BTN2A1	NM_078476.4		c.557C>T	p.Ala186Val	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.557C>T	p.Ala186Val	missense	Exon 4 of 8	ENSP00000312158.5	Q7KYR7-2
	BTN2A1	ENST00000429381.5	TSL:1	c.557C>T	p.Ala186Val	missense	Exon 4 of 8	ENSP00000416945.1	Q7KYR7-4
	BTN2A1	ENST00000469185.5	TSL:1	c.557C>T	p.Ala186Val	missense	Exon 4 of 8	ENSP00000419043.1	Q7KYR7-6

Frequencies

GnomAD3 genomes AF: 0.000250 AC: 38 AN: 152042 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000870

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000835 AC: 21 AN: 251462 AF XY: 0.0000662

Gnomad AFR exome AF: 0.000923

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000424 AC: 62 AN: 1461894 Hom.: 0 Cov.: 31 AF XY: 0.0000468 AC XY: 34 AN XY: 727248

African (AFR) AF: 0.00108 AC: 36 AN: 33480

American (AMR) AF: 0.0000671 AC: 3 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000144 AC: 16 AN: 1112012

Other (OTH) AF: 0.0000497 AC: 3 AN: 60396

GnomAD4 genome AF: 0.000250 AC: 38 AN: 152042 Hom.: 0 Cov.: 31 AF XY: 0.000189 AC XY: 14 AN XY: 74254

African (AFR) AF: 0.000870 AC: 36 AN: 41402

American (AMR) AF: 0.0000655 AC: 1 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000118 Hom.: 0

Bravo AF: 0.000261

ESP6500AA AF: 0.00136 AC: 6

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000988 AC: 12

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	1.1
DANN	Benign	0.081
DEOGEN2	Benign	0.00014	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0012	N
LIST_S2	Benign	0.064	T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.0078	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-2.8	N
PhyloP100		0.75
PrimateAI	Benign	0.25	T
PROVEAN	Benign	2.1	N
REVEL	Benign	0.057
Sift	Benign	1.0	T
Sift4G	Benign	0.53	T
Polyphen		0.0	B
Vest4		0.056
MVP		0.25
MPC		0.067
ClinPred		0.014	T
GERP RS		0.47
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.079
gMVP		0.072
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs139773763; hg19: chr6-26463598;