6-26459601-G-A

Variant names:

• chr6-26459601-G-A
• rs149038955
• NM_007049.5:c.203G>A

Variant summary

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

The NM_007049.5(BTN2A1):​c.203G>A​(p.Arg68Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000149 in 1,613,828 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R68P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00026 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00014 (0 hom.)
• Consequence: BTN2A1 NM_007049.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.45
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.13984752).

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.203G>A	p.Arg68Gln	missense	Exon 3 of 8	NP_008980.1	Q7KYR7-2
	BTN2A1	NM_001197233.3		c.20G>A	p.Arg7Gln	missense	Exon 2 of 7	NP_001184162.1	Q7KYR7-5
	BTN2A1	NM_078476.4		c.203G>A	p.Arg68Gln	missense	Exon 3 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.203G>A	p.Arg68Gln	missense	Exon 3 of 8	ENSP00000312158.5	Q7KYR7-2
	BTN2A1	ENST00000429381.5	TSL:1	c.203G>A	p.Arg68Gln	missense	Exon 3 of 8	ENSP00000416945.1	Q7KYR7-4
	BTN2A1	ENST00000469185.5	TSL:1	c.203G>A	p.Arg68Gln	missense	Exon 3 of 8	ENSP00000419043.1	Q7KYR7-6

Frequencies

GnomAD3 genomes AF: 0.000257 AC: 39 AN: 151946 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000677

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

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: 0.000118

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000795 AC: 20 AN: 251486 AF XY: 0.0000441

Gnomad AFR exome AF: 0.000738

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000527

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000137 AC: 201 AN: 1461882 Hom.: 0 Cov.: 32 AF XY: 0.000124 AC XY: 90 AN XY: 727240

African (AFR) AF: 0.000597 AC: 20 AN: 33476

American (AMR) AF: 0.0000224 AC: 1 AN: 44722

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

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

South Asian (SAS) AF: 0.0000116 AC: 1 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: 0.000150 AC: 167 AN: 1112010

Other (OTH) AF: 0.000199 AC: 12 AN: 60392

GnomAD4 genome AF: 0.000257 AC: 39 AN: 151946 Hom.: 0 Cov.: 31 AF XY: 0.000175 AC XY: 13 AN XY: 74194

African (AFR) AF: 0.000677 AC: 28 AN: 41348

American (AMR) AF: 0.000131 AC: 2 AN: 15250

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10582

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

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 67982

Other (OTH) AF: 0.000478 AC: 1 AN: 2090

Alfa AF: 0.000197 Hom.: 0

Bravo AF: 0.000287

ESP6500AA AF: 0.00136 AC: 6

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000107 AC: 13

EpiCase AF: 0.000109

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	0.11
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.17
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.034	T
Eigen	Benign	0.17
Eigen_PC	Benign	0.11
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.83	T
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		3.4
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-3.0	D
REVEL	Uncertain	0.47
Sift	Benign	0.034	D
Sift4G	Uncertain	0.026	D
Polyphen		0.92	P
Vest4		0.31
MVP		0.73
MPC		0.30
ClinPred		0.22	T
GERP RS		3.0
Varity_R		0.20
gMVP		0.50
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs149038955; hg19: chr6-26459829;