rs2242400

Variant names:

• chr12-24945140-A-G
• rs2242400
• NM_005504.7:c.6+3787T>C

Variant summary

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

The NM_005504.7(BCAT1):​c.6+3787T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 152,222 control chromosomes in the GnomAD database, including 1,867 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 0.15 (1867 hom., cov: 32)
• Consequence: BCAT1 NM_005504.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.244
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.236 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCAT1	NM_005504.7	c.6+3787T>C		intron_variant	Intron 1 of 10	ENST00000261192.12	NP_005495.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCAT1	ENST00000261192.12	c.6+3787T>C		intron_variant	Intron 1 of 10	1	NM_005504.7	ENSP00000261192.7
BCAT1	ENST00000539780.5	c.6+3787T>C		intron_variant	Intron 1 of 9	2		ENSP00000440827.1
BCAT1	ENST00000342945.9	c.6+3787T>C		intron_variant	Intron 1 of 8	2		ENSP00000339805.5
BCAT1	ENST00000546285.1	c.6+3787T>C		intron_variant	Intron 1 of 3	4		ENSP00000438593.1

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22336 AN: 152102 Hom.: 1868 Cov.: 32

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.248

Gnomad SAS AF: 0.0614

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.153

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

GnomAD4 genome AF: 0.147 AC: 22338 AN: 152222 Hom.: 1867 Cov.: 32 AF XY: 0.149 AC XY: 11120 AN XY: 74430

African (AFR) AF: 0.181 AC: 7521 AN: 41512

American (AMR) AF: 0.209 AC: 3201 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 462 AN: 3470

East Asian (EAS) AF: 0.248 AC: 1284 AN: 5186

South Asian (SAS) AF: 0.0608 AC: 294 AN: 4832

European-Finnish (FIN) AF: 0.155 AC: 1648 AN: 10608

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.109 AC: 7405 AN: 67996

Other (OTH) AF: 0.152 AC: 321 AN: 2116

Alfa AF: 0.121 Hom.: 2578

Bravo AF: 0.156

Asia WGS AF: 0.133 AC: 464 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.9
DANN	Benign	0.64
PhyloP100		-0.24
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: rs2242400; hg19: chr12-25098074;