Genetic Variant NM_007049.5:c.238G>T (chr6-26459636-G-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_007049.5(BTN2A1):c.238G>T(p.Gly80Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000088 in 1,614,144 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00050 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000045 ( 0 hom. )

Consequence

BTN2A1
NM_007049.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.402

Publications

1 publications found

Variant links:

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]

BTN2A1 links:

ENSG00000291336 (HGNC:):

ENSG00000291336 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.036928445).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BTN2A1	NM_007049.5	MANE Select	c.238G>T	p.Gly80Cys	missense	Exon 3 of 8	NP_008980.1	Q7KYR7-2
BTN2A1	NM_001197233.3		c.55G>T	p.Gly19Cys	missense	Exon 2 of 7	NP_001184162.1	Q7KYR7-5
BTN2A1	NM_078476.4		c.238G>T	p.Gly80Cys	missense	Exon 3 of 8	NP_510961.1	Q7KYR7-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BTN2A1	ENST00000312541.10	TSL:1 MANE Select	c.238G>T	p.Gly80Cys	missense	Exon 3 of 8	ENSP00000312158.5	Q7KYR7-2
BTN2A1	ENST00000429381.5	TSL:1	c.238G>T	p.Gly80Cys	missense	Exon 3 of 8	ENSP00000416945.1	Q7KYR7-4
BTN2A1	ENST00000469185.5	TSL:1	c.238G>T	p.Gly80Cys	missense	Exon 3 of 8	ENSP00000419043.1	Q7KYR7-6

Frequencies

GnomAD3 genomes

AF:

0.000500

AC:

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00157

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000459

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:

0.0000294

Gnomad OTH

AF:

0.000956

GnomAD2 exomes

AF:

0.0000835

AC:

AN:

251488

AF XY:

0.0000662

show subpopulations

Gnomad AFR exome

AF:

0.00117

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000451

AC:

AN:

1461894

Hom.:

Cov.:

AF XY:

0.0000440

AC XY:

AN XY:

727248

show subpopulations

African (AFR)

AF:

0.00149

AC:

AN:

33480

American (AMR)

AF:

0.000112

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1112012

Other (OTH)

AF:

0.000116

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000499

AC:

AN:

152250

Hom.:

Cov.:

AF XY:

0.000524

AC XY:

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.00156

AC:

AN:

41554

American (AMR)

AF:

0.000458

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68004

Other (OTH)

AF:

0.000946

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000131

Hom.:

Bravo

AF:

0.000544

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000906

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.25

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.22

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.86

M_CAP

Uncertain

0.099

MetaRNN

Benign

0.037

MetaSVM

Benign

-0.82

MutationAssessor

Uncertain

2.8

PhyloP100

0.40

PrimateAI

Benign

0.32

PROVEAN

Uncertain

-3.9

REVEL

Benign

0.21

Sift

Uncertain

0.012

Sift4G

Uncertain

0.018

Polyphen

1.0

Vest4

0.46

MVP

0.64

MPC

0.40

ClinPred

0.17

GERP RS

2.1

Varity_R

0.90

gMVP

0.37

Mutation Taster

=95/5

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over