dbSNP rs73587806: BCAT2:c.*74C>T (chr19-48795352-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001190.4(BCAT2):c.*74C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00267 in 1,593,248 control chromosomes in the GnomAD database, including 92 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 0.014 ( 49 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 43 hom. )

Consequence

BCAT2
NM_001190.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.83

Publications

3 publications found

Variant links:

Genes affected

BCAT2 (HGNC:977): (branched chain amino acid transaminase 2) This gene encodes a branched chain aminotransferase found in mitochondria. The encoded protein forms a dimer that catalyzes the first step in the production of the branched chain amino acids leucine, isoleucine, and valine. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

BCAT2 Gene-Disease associations (from GenCC):

hypervalinemia and hyperleucine-isoleucinemia
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen

BCAT2 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 (BayesDel_noAF=-0.48).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0141 (2140/152280) while in subpopulation AFR AF = 0.0479 (1989/41548). AF 95% confidence interval is 0.0461. There are 49 homozygotes in GnomAd4. There are 999 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 49 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
BCAT2	NM_001190.4 link	c.*74C>T	3_prime_UTR_variant	Exon 11 of 11	ENST00000316273.11	NP_001181.2	O15382-1
BCAT2	NM_001284325.2 link	c.*74C>T	3_prime_UTR_variant	Exon 12 of 12		NP_001271254.1	O15382B3KSI3
BCAT2	NM_001164773.2 link	c.*74C>T	3_prime_UTR_variant	Exon 9 of 9		NP_001158245.1	O15382-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCAT2	ENST00000316273.11 link	c.*74C>T		3_prime_UTR_variant	Exon 11 of 11	1	NM_001190.4	ENSP00000322991.5		O15382-1

Frequencies

GnomAD3 genomes

AF:

0.0140

AC:

2136

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0479

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00662

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.000963

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.0115

GnomAD4 exome

AF:

0.00147

AC:

2121

AN:

1440968

Hom.:

Cov.:

AF XY:

0.00131

AC XY:

942

AN XY:

717718

show subpopulations

African (AFR)

AF:

0.0479

AC:

1582

AN:

33012

American (AMR)

AF:

0.00269

AC:

119

AN:

44272

Ashkenazi Jewish (ASJ)

AF:

0.000656

AC:

AN:

25910

East Asian (EAS)

AF:

0.000507

AC:

AN:

39454

South Asian (SAS)

AF:

0.000164

AC:

AN:

85386

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52192

Middle Eastern (MID)

AF:

0.00122

AC:

AN:

5730

European-Non Finnish (NFE)

AF:

0.000124

AC:

136

AN:

1095266

Other (OTH)

AF:

0.00378

AC:

226

AN:

59746

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

103

205

308

410

513

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

150

200

250

<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:

0.0141

AC:

2140

AN:

152280

Hom.:

Cov.:

AF XY:

0.0134

AC XY:

999

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.0479

AC:

1989

AN:

41548

American (AMR)

AF:

0.00654

AC:

100

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00144

AC:

AN:

3470

East Asian (EAS)

AF:

0.000965

AC:

AN:

5180

South Asian (SAS)

AF:

0.000414

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000132

AC:

AN:

68030

Other (OTH)

AF:

0.0123

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

102

204

305

407

509

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<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:

0.00452

Hom.:

Bravo

AF:

0.0159

Asia WGS

AF:

0.0120

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.96

PhyloP100

1.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism

(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