rs12579934

chr12-24911484-G-Achr12-24911484-G-Cchr12-24911484-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005504.7(BCAT1):c.7-9599C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 152,098 control chromosomes in the GnomAD database, including 12,698 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 0.40 (12698 hom., cov: 33)
• Consequence: BCAT1 NM_005504.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.533

Genes affected

BCAT1 (HGNC:976): (branched chain amino acid transaminase 1) This gene encodes the cytosolic form of the enzyme branched-chain amino acid transaminase. This enzyme catalyzes the reversible transamination of branched-chain alpha-keto acids to branched-chain L-amino acids essential for cell growth. Two different clinical disorders have been attributed to a defect of branched-chain amino acid transamination: hypervalinemia and hyperleucine-isoleucinemia. As there is also a gene encoding a mitochondrial form of this enzyme, mutations in either gene may contribute to these disorders. Alternatively spliced transcript variants have been described. [provided by RefSeq, May 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCAT1	NM_005504.7	c.7-9599C>T		intron_variant		ENST00000261192.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCAT1	ENST00000261192.12	c.7-9599C>T		intron_variant		1	NM_005504.7	P1
BCAT1	ENST00000342945.9	c.7-17009C>T		intron_variant		2
BCAT1	ENST00000539780.5	c.7-9599C>T		intron_variant		2
BCAT1	ENST00000546285.1	c.7-17009C>T		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.405 AC: 61489 AN: 151978 Hom.: 12683 Cov.: 33

Gnomad AFR AF: 0.437

Gnomad AMI AF: 0.454

Gnomad AMR AF: 0.356

Gnomad ASJ AF: 0.509

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.407

Gnomad OTH AF: 0.433

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.405 AC: 61540 AN: 152098 Hom.: 12698 Cov.: 33 AF XY: 0.398 AC XY: 29574 AN XY: 74348

Gnomad4 AFR AF: 0.437

Gnomad4 AMR AF: 0.356

Gnomad4 ASJ AF: 0.509

Gnomad4 EAS AF: 0.473

Gnomad4 SAS AF: 0.342

Gnomad4 FIN AF: 0.279

Gnomad4 NFE AF: 0.407

Gnomad4 OTH AF: 0.430

Alfa AF: 0.389 Hom.: 6319

Bravo AF: 0.416

Asia WGS AF: 0.385 AC: 1338 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	9.0
Dann	Benign	0.73

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: rs12579934; hg19: chr12-25064418;