Genetic Variant NM_007049.5:c.-136T>C (chr6-26458037-T-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_007049.5(BTN2A1):c.-136T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.708 in 152,156 control chromosomes in the GnomAD database, including 40,102 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.71 ( 40102 hom., cov: 33)

Exomes 𝑓: 0.79 ( 67 hom. )

Failed GnomAD Quality Control

Consequence

BTN2A1
NM_007049.5 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0850

Publications

39 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:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.891 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
BTN2A1	NM_007049.5 link	c.-136T>C	5_prime_UTR_variant	Exon 1 of 8	ENST00000312541.10	NP_008980.1	Q7KYR7-2
BTN2A1	NM_001197233.3 link	c.-207T>C	5_prime_UTR_variant	Exon 1 of 7		NP_001184162.1	Q7KYR7-5
BTN2A1	NM_078476.4 link	c.-136T>C	5_prime_UTR_variant	Exon 1 of 8		NP_510961.1	Q7KYR7-4
BTN2A1	NM_001197234.3 link	c.-136T>C	5_prime_UTR_variant	Exon 1 of 8		NP_001184163.1	Q7KYR7-6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BTN2A1	ENST00000312541.10 link	c.-136T>C		5_prime_UTR_variant	Exon 1 of 8	1	NM_007049.5	ENSP00000312158.5		Q7KYR7-2

Frequencies

GnomAD3 genomes

AF:

0.709

AC:

107730

AN:

152038

Hom.:

40092

Cov.:

show subpopulations

Gnomad AFR

AF:

0.467

Gnomad AMI

AF:

0.791

Gnomad AMR

AF:

0.712

Gnomad ASJ

AF:

0.730

Gnomad EAS

AF:

0.913

Gnomad SAS

AF:

0.778

Gnomad FIN

AF:

0.834

Gnomad MID

AF:

0.734

Gnomad NFE

AF:

0.812

Gnomad OTH

AF:

0.701

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.789

AC:

161

AN:

204

Hom.:

Cov.:

AF XY:

0.794

AC XY:

108

AN XY:

136

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AF:

0.788

AC:

AN:

European-Finnish (FIN)

AF:

0.750

AC:

AN:

Middle Eastern (MID)

AF:

1.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.795

AC:

AN:

112

Other (OTH)

AF:

0.750

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.708

AC:

107768

AN:

152156

Hom.:

40102

Cov.:

AF XY:

0.711

AC XY:

52928

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.467

AC:

19379

AN:

41484

American (AMR)

AF:

0.712

AC:

10890

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.730

AC:

2533

AN:

3472

East Asian (EAS)

AF:

0.913

AC:

4721

AN:

5170

South Asian (SAS)

AF:

0.777

AC:

3746

AN:

4822

European-Finnish (FIN)

AF:

0.834

AC:

8855

AN:

10614

Middle Eastern (MID)

AF:

0.728

AC:

214

AN:

294

European-Non Finnish (NFE)

AF:

0.812

AC:

55228

AN:

67998

Other (OTH)

AF:

0.704

AC:

1482

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1456

2912

4369

5825

7281

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

826

1652

2478

3304

4130

<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:

0.767

Hom.:

66864

Bravo

AF:

0.685

Asia WGS

AF:

0.828

AC:

2879

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

6.6

(source)

DANN

Benign

0.65

PhyloP100

0.085

PromoterAI

0.033

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=300/0

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