19-48799813-G-C

Variant names:

• chr19-48799813-G-C
• rs11548193
• NM_001190.4:c.557C>G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001190.4(BCAT2):​c.557C>G​(p.Thr186Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 1,558,204 control chromosomes in the GnomAD database, including 32,136 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.14 (2071 hom., cov: 32)
  • Exomes 𝑓: 0.20 (30065 hom.)
• Consequence: BCAT2 NM_001190.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.38

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0057376027).
• BP6: Variant 19-48799813-G-C is Benign according to our data. Variant chr19-48799813-G-C is described in ClinVar as [Benign]. Clinvar id is 1601520.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCAT2	NM_001190.4	c.557C>G	p.Thr186Arg	missense_variant	Exon 6 of 11	ENST00000316273.11	NP_001181.2
BCAT2	NM_001284325.2	c.437C>G	p.Thr146Arg	missense_variant	Exon 7 of 12		NP_001271254.1
BCAT2	NM_001164773.2	c.281C>G	p.Thr94Arg	missense_variant	Exon 4 of 9		NP_001158245.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCAT2	ENST00000316273.11	c.557C>G	p.Thr186Arg	missense_variant	Exon 6 of 11	1	NM_001190.4	ENSP00000322991.5

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21680 AN: 152104 Hom.: 2073 Cov.: 32

Gnomad AFR AF: 0.0407

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0741

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.157

GnomAD3 exomes AF: 0.143 AC: 23300 AN: 163330 Hom.: 2115 AF XY: 0.144 AC XY: 12508 AN XY: 86676

Gnomad AFR exome AF: 0.0337

Gnomad AMR exome AF: 0.0958

Gnomad ASJ exome AF: 0.165

Gnomad EAS exome AF: 0.000500

Gnomad SAS exome AF: 0.0831

Gnomad FIN exome AF: 0.173

Gnomad NFE exome AF: 0.213

Gnomad OTH exome AF: 0.166

GnomAD4 exome AF: 0.197 AC: 276976 AN: 1405982 Hom.: 30065 Cov.: 33 AF XY: 0.194 AC XY: 134382 AN XY: 694160

Gnomad4 AFR exome AF: 0.0315

Gnomad4 AMR exome AF: 0.0986

Gnomad4 ASJ exome AF: 0.170

Gnomad4 EAS exome AF: 0.000438

Gnomad4 SAS exome AF: 0.0843

Gnomad4 FIN exome AF: 0.176

Gnomad4 NFE exome AF: 0.223

Gnomad4 OTH exome AF: 0.180

GnomAD4 genome AF: 0.142 AC: 21677 AN: 152222 Hom.: 2071 Cov.: 32 AF XY: 0.139 AC XY: 10312 AN XY: 74432

Gnomad4 AFR AF: 0.0406

Gnomad4 AMR AF: 0.132

Gnomad4 ASJ AF: 0.187

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0746

Gnomad4 FIN AF: 0.170

Gnomad4 NFE AF: 0.214

Gnomad4 OTH AF: 0.155

Alfa AF: 0.188 Hom.: 977

Bravo AF: 0.136

TwinsUK AF: 0.213 AC: 790

ALSPAC AF: 0.227 AC: 875

ESP6500AA AF: 0.0438 AC: 187

ESP6500EA AF: 0.197 AC: 1658

ExAC AF: 0.0967 AC: 10685

Asia WGS AF: 0.0350 AC: 123 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	11
DANN	Benign	0.73
DEOGEN2	Benign	0.29	.;T;T;T;T;T;T
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.058	N
LIST_S2	Uncertain	0.95	D;.;D;D;D;D;D
MetaRNN	Benign	0.0057	T;T;T;T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.4	.;.;L;.;.;.;.
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.7	N;N;N;.;.;.;.
REVEL	Benign	0.040
Sift	Benign	0.47	T;T;T;.;.;.;.
Sift4G	Benign	0.49	T;T;T;T;T;T;T
Polyphen		0.015	B;B;B;.;B;.;.
Vest4		0.25
MPC		0.50
ClinPred		0.015	T
GERP RS		2.0
Varity_R		0.18
gMVP		0.63

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

LitVar

Other links and lift over

dbSNP: rs11548193; hg19: chr19-49303070; COSMIC: COSV60271830; COSMIC: COSV60271830;