12-24811449-T-C

Variant names:

• chr12-24811449-T-C
• rs1043881
• NM_005504.7:c.*6559A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005504.7(BCAT1):​c.*6559A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 152,120 control chromosomes in the GnomAD database, including 3,927 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 0.20 (3927 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: BCAT1 NM_005504.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.283
• Publications: 11 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=-0.55).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.662 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.*6559A>G		3_prime_UTR	Exon 11 of 11	NP_005495.2
	BCAT1	NR_182105.1		n.5573A>G		non_coding_transcript_exon	Exon 12 of 12
	BCAT1	NR_182106.1		n.7725A>G		non_coding_transcript_exon	Exon 10 of 10

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCAT1	ENST00000261192.12	TSL:1 MANE Select	c.*6559A>G		3_prime_UTR	Exon 11 of 11	ENSP00000261192.7

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29842 AN: 152002 Hom.: 3922 Cov.: 32

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.263

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.681

Gnomad SAS AF: 0.382

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.242

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.197

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.196 AC: 29857 AN: 152120 Hom.: 3927 Cov.: 32 AF XY: 0.204 AC XY: 15151 AN XY: 74380

African (AFR) AF: 0.129 AC: 5337 AN: 41528

American (AMR) AF: 0.263 AC: 4012 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 609 AN: 3470

East Asian (EAS) AF: 0.680 AC: 3523 AN: 5178

South Asian (SAS) AF: 0.380 AC: 1834 AN: 4822

European-Finnish (FIN) AF: 0.177 AC: 1872 AN: 10590

Middle Eastern (MID) AF: 0.247 AC: 72 AN: 292

European-Non Finnish (NFE) AF: 0.176 AC: 11971 AN: 67950

Other (OTH) AF: 0.204 AC: 431 AN: 2112

Alfa AF: 0.183 Hom.: 3449

Bravo AF: 0.202

Asia WGS AF: 0.505 AC: 1750 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	11
DANN	Benign	0.81
PhyloP100		0.28
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs1043881; hg19: chr12-24964383;