19-48799813-G-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• 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
• Publications: 39 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001190.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCAT2	ENST00000316273.11	TSL:1 MANE Select	c.557C>G	p.Thr186Arg	missense	Exon 6 of 11	ENSP00000322991.5
	BCAT2	ENST00000598162.5	TSL:1	c.557C>G	p.Thr186Arg	missense	Exon 6 of 10	ENSP00000470216.1
	BCAT2	ENST00000599246.5	TSL:1	c.281C>G	p.Thr94Arg	missense	Exon 4 of 8	ENSP00000470680.1

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

GnomAD2 exomes AF: 0.143 AC: 23300 AN: 163330 AF XY: 0.144

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 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

African (AFR) AF: 0.0315 AC: 1012 AN: 32164

American (AMR) AF: 0.0986 AC: 3543 AN: 35946

Ashkenazi Jewish (ASJ) AF: 0.170 AC: 4270 AN: 25188

East Asian (EAS) AF: 0.000438 AC: 16 AN: 36564

South Asian (SAS) AF: 0.0843 AC: 6742 AN: 80014

European-Finnish (FIN) AF: 0.176 AC: 8681 AN: 49248

Middle Eastern (MID) AF: 0.148 AC: 841 AN: 5698

European-Non Finnish (NFE) AF: 0.223 AC: 241366 AN: 1082892

Other (OTH) AF: 0.180 AC: 10505 AN: 58268

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

African (AFR) AF: 0.0406 AC: 1687 AN: 41556

American (AMR) AF: 0.132 AC: 2013 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.187 AC: 648 AN: 3472

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5182

South Asian (SAS) AF: 0.0746 AC: 360 AN: 4826

European-Finnish (FIN) AF: 0.170 AC: 1807 AN: 10608

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.214 AC: 14561 AN: 67980

Other (OTH) AF: 0.155 AC: 327 AN: 2108

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

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.058	N
LIST_S2	Uncertain	0.95	D
MetaRNN	Benign	0.0057	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.4	L
PhyloP100		1.4
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.040
Sift	Benign	0.47	T
Sift4G	Benign	0.49	T
Polyphen		0.015	B
Vest4		0.25
MPC		0.50
ClinPred		0.015	T
GERP RS		2.0
Varity_R		0.18
gMVP		0.63
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

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