rs144358349

Variant names:

• chr6-26463408-G-A
• rs144358349
• NM_007049.5:c.595G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-26463408-G-A
• chr6-26463408-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_007049.5(BTN2A1):​c.595G>A​(p.Gly199Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000113 in 1,614,118 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00012 (1 hom.)
• Consequence: BTN2A1 NM_007049.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.43
• Publications: 3 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.12674662).

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.595G>A	p.Gly199Ser	missense	Exon 4 of 8	NP_008980.1	Q7KYR7-2
	BTN2A1	NM_001197233.3		c.412G>A	p.Gly138Ser	missense	Exon 3 of 7	NP_001184162.1	Q7KYR7-5
	BTN2A1	NM_078476.4		c.595G>A	p.Gly199Ser	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.595G>A	p.Gly199Ser	missense	Exon 4 of 8	ENSP00000312158.5	Q7KYR7-2
	BTN2A1	ENST00000429381.5	TSL:1	c.595G>A	p.Gly199Ser	missense	Exon 4 of 8	ENSP00000416945.1	Q7KYR7-4
	BTN2A1	ENST00000469185.5	TSL:1	c.595G>A	p.Gly199Ser	missense	Exon 4 of 8	ENSP00000419043.1	Q7KYR7-6

Frequencies

GnomAD3 genomes AF: 0.0000592 AC: 9 AN: 152108 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000915 AC: 23 AN: 251480 AF XY: 0.000125

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000114

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000118 AC: 173 AN: 1461892 Hom.: 1 Cov.: 31 AF XY: 0.000129 AC XY: 94 AN XY: 727246

African (AFR) AF: 0.000119 AC: 4 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 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: 0.000417 AC: 36 AN: 86258

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

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.000107 AC: 119 AN: 1112010

Other (OTH) AF: 0.000182 AC: 11 AN: 60396

GnomAD4 genome AF: 0.0000591 AC: 9 AN: 152226 Hom.: 0 Cov.: 31 AF XY: 0.0000806 AC XY: 6 AN XY: 74426

African (AFR) AF: 0.0000241 AC: 1 AN: 41548

American (AMR) AF: 0.00 AC: 0 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5170

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 67998

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.0000965 Hom.: 0

Bravo AF: 0.0000491

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000132 AC: 16

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.57
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.038	T
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.25
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		2.4
PrimateAI	Benign	0.37	T
PROVEAN	Pathogenic	-5.0	D
REVEL	Benign	0.095
Sift	Benign	0.041	D
Sift4G	Uncertain	0.036	D
Polyphen		0.98	D
Vest4		0.23
MVP		0.26
MPC		0.34
ClinPred		0.77	D
GERP RS		1.1
Varity_R		0.23
gMVP		0.46
Mutation Taster		=89/11	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

Other links and lift over

dbSNP: rs144358349; hg19: chr6-26463636;