chr12-24911484-G-A

Variant names:

• chr12-24911484-G-A
• rs12579934
• NM_005504.7:c.7-9599C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005504.7. 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
	BCAT1	NM_005504.7	MANE Select	c.7-9599C>T		intron	N/A	NP_005495.2
	BCAT1	NM_001413094.1		c.7-17009C>T		intron	N/A	NP_001400023.1
	BCAT1	NM_001178091.2		c.7-9599C>T		intron	N/A	NP_001171562.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCAT1	ENST00000261192.12	TSL:1 MANE Select	c.7-9599C>T		intron	N/A	ENSP00000261192.7
	BCAT1	ENST00000539780.5	TSL:2	c.7-9599C>T		intron	N/A	ENSP00000440827.1
	BCAT1	ENST00000342945.9	TSL:2	c.7-17009C>T		intron	N/A	ENSP00000339805.5

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

African (AFR) AF: 0.437 AC: 18131 AN: 41484

American (AMR) AF: 0.356 AC: 5434 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.509 AC: 1767 AN: 3470

East Asian (EAS) AF: 0.473 AC: 2451 AN: 5178

South Asian (SAS) AF: 0.342 AC: 1649 AN: 4822

European-Finnish (FIN) AF: 0.279 AC: 2953 AN: 10570

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.407 AC: 27695 AN: 67980

Other (OTH) AF: 0.430 AC: 908 AN: 2114

Alfa AF: 0.406 Hom.: 26257

Bravo AF: 0.416

Asia WGS AF: 0.385 AC: 1338 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	9.0
DANN	Benign	0.73
PhyloP100		0.53
Mutation Taster		=100/0	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: rs12579934; hg19: chr12-25064418;