Genetic Variant NM_007048.6:c.845G>C (chr6-26409662-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_007048.6(BTN3A1):c.845G>C(p.Arg282Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0778 in 1,599,422 control chromosomes in the GnomAD database, including 6,272 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.047 ( 255 hom., cov: 31)

Exomes 𝑓: 0.081 ( 6017 hom. )

Consequence

BTN3A1
NM_007048.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -5.25

Publications

41 publications found

Variant links:

Genes affected

BTN3A1 (HGNC:1138): (butyrophilin subfamily 3 member A1) The butyrophilin (BTN) genes are a group of major histocompatibility complex (MHC)-associated genes that encode type I membrane proteins with 2 extracellular immunoglobulin (Ig) domains and an intracellular B30.2 (PRYSPRY) domain. Three subfamilies of human BTN genes are located in the MHC class I region: the single-copy BTN1A1 gene (MIM 601610) and the BTN2 (e.g., BTN2A1; MIM 613590) and BTN3 (e.g., BNT3A1) genes, which have undergone tandem duplication, resulting in 3 copies of each (summary by Smith et al., 2010 [PubMed 20208008]).[supplied by OMIM, Nov 2010]

BTN3A1 links:

ENSG00000291336 (HGNC:):

ENSG00000291336 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0023488998).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0795 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTN3A1	NM_007048.6 link	c.845G>C	p.Arg282Thr	missense_variant	Exon 5 of 10	ENST00000289361.11	NP_008979.3	O00481-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BTN3A1	ENST00000289361.11 link	c.845G>C	p.Arg282Thr	missense_variant	Exon 5 of 10	1	NM_007048.6	ENSP00000289361.6		O00481-1

Frequencies

GnomAD3 genomes

AF:

0.0466

AC:

7087

AN:

152080

Hom.:

255

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0129

Gnomad AMI

AF:

0.113

Gnomad AMR

AF:

0.0244

Gnomad ASJ

AF:

0.0199

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.0386

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0813

Gnomad OTH

AF:

0.0330

GnomAD2 exomes

AF:

0.0446

AC:

10575

AN:

236930

AF XY:

0.0443

show subpopulations

Gnomad AFR exome

AF:

0.0132

Gnomad AMR exome

AF:

0.0172

Gnomad ASJ exome

AF:

0.0199

Gnomad EAS exome

AF:

0.0000586

Gnomad FIN exome

AF:

0.0400

Gnomad NFE exome

AF:

0.0791

Gnomad OTH exome

AF:

0.0433

GnomAD4 exome

AF:

0.0810

AC:

117282

AN:

1447224

Hom.:

6017

Cov.:

AF XY:

0.0778

AC XY:

56049

AN XY:

720750

show subpopulations

African (AFR)

AF:

0.0116

AC:

370

AN:

32030

American (AMR)

AF:

0.0172

AC:

681

AN:

39580

Ashkenazi Jewish (ASJ)

AF:

0.0204

AC:

511

AN:

24992

East Asian (EAS)

AF:

0.0000757

AC:

AN:

39642

South Asian (SAS)

AF:

0.000129

AC:

AN:

85596

European-Finnish (FIN)

AF:

0.0399

AC:

2109

AN:

52908

Middle Eastern (MID)

AF:

0.00320

AC:

AN:

5620

European-Non Finnish (NFE)

AF:

0.0991

AC:

109708

AN:

1107398

Other (OTH)

AF:

0.0651

AC:

3871

AN:

59458

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

6122

12244

18366

24488

30610

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4128

8256

12384

16512

20640

<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:

0.0465

AC:

7082

AN:

152198

Hom.:

255

Cov.:

AF XY:

0.0422

AC XY:

3137

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.0129

AC:

534

AN:

41540

American (AMR)

AF:

0.0243

AC:

371

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0199

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.000208

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.0386

AC:

410

AN:

10610

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0813

AC:

5524

AN:

67976

Other (OTH)

AF:

0.0327

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

342

684

1027

1369

1711

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

168

252

336

420

<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:

0.0675

Hom.:

350

Bravo

AF:

0.0442

TwinsUK

AF:

0.121

AC:

447

ALSPAC

AF:

0.107

AC:

413

ESP6500AA

AF:

0.0179

AC:

ESP6500EA

AF:

0.0815

AC:

701

ExAC

AF:

0.0445

AC:

5407

Asia WGS

AF:

0.00433

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.66

CADD

Benign

0.0050

(source)

DANN

Benign

0.56

DEOGEN2

Benign

0.0057

.;T;.;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0059

LIST_S2

Benign

0.32

T;T;T;T

MetaRNN

Benign

0.0023

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

M;M;M;.

PhyloP100

-5.2

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.69

N;N;N;N

REVEL

Benign

0.015

Sift

Benign

0.11

T;T;T;T

Sift4G

Benign

0.24

T;T;T;T

Polyphen

0.0

B;B;B;.

Vest4

0.070

MPC

0.080

ClinPred

0.0060

GERP RS

-1.3

Varity_R

0.023

gMVP

0.12

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over