NM_001190.4:c.1065+8G>A

Variant names:

• chr19-48796570-C-T
• rs35829476
• NM_001190.4:c.1065+8G>A

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.1065+8G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0472 in 1,611,944 control chromosomes in the GnomAD database, including 1,965 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.048 (196 hom., cov: 33)
  • Exomes 𝑓: 0.047 (1769 hom.)
• Consequence: BCAT2 NM_001190.4 splice_region, intron
• Scores: Splicing: ADA: 0.0002320
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.76
• Publications: 8 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 (BayesDel_noAF=-0.82).
• BP6: Variant 19-48796570-C-T is Benign according to our data. Variant chr19-48796570-C-T is described in ClinVar as Benign. ClinVar VariationId is 1666580.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0691 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCAT2	NM_001190.4	MANE Select	c.1065+8G>A		splice_region intron	N/A	NP_001181.2	O15382-1
	BCAT2	NM_001284325.2		c.945+8G>A		splice_region intron	N/A	NP_001271254.1	B3KSI3
	BCAT2	NM_001164773.2		c.789+8G>A		splice_region intron	N/A	NP_001158245.1	O15382-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCAT2	ENST00000316273.11	TSL:1 MANE Select	c.1065+8G>A		splice_region intron	N/A	ENSP00000322991.5	O15382-1
	BCAT2	ENST00000598162.5	TSL:1	c.1065+8G>A		splice_region intron	N/A	ENSP00000470216.1	M0QZ10
	BCAT2	ENST00000599246.5	TSL:1	c.789+8G>A		splice_region intron	N/A	ENSP00000470680.1	M0QZP4

Frequencies

GnomAD3 genomes AF: 0.0474 AC: 7216 AN: 152138 Hom.: 191 Cov.: 33

Gnomad AFR AF: 0.0505

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0392

Gnomad ASJ AF: 0.0784

Gnomad EAS AF: 0.0316

Gnomad SAS AF: 0.0248

Gnomad FIN AF: 0.0470

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0491

Gnomad OTH AF: 0.0522

GnomAD2 exomes AF: 0.0441 AC: 10981 AN: 249064 AF XY: 0.0439

Gnomad AFR exome AF: 0.0513

Gnomad AMR exome AF: 0.0269

Gnomad ASJ exome AF: 0.0762

Gnomad EAS exome AF: 0.0304

Gnomad FIN exome AF: 0.0444

Gnomad NFE exome AF: 0.0510

Gnomad OTH exome AF: 0.0546

GnomAD4 exome AF: 0.0472 AC: 68849 AN: 1459688 Hom.: 1769 Cov.: 35 AF XY: 0.0470 AC XY: 34097 AN XY: 726104

African (AFR) AF: 0.0528 AC: 1767 AN: 33468

American (AMR) AF: 0.0283 AC: 1265 AN: 44632

Ashkenazi Jewish (ASJ) AF: 0.0763 AC: 1988 AN: 26046

East Asian (EAS) AF: 0.0334 AC: 1327 AN: 39688

South Asian (SAS) AF: 0.0291 AC: 2503 AN: 86098

European-Finnish (FIN) AF: 0.0446 AC: 2335 AN: 52378

Middle Eastern (MID) AF: 0.0749 AC: 432 AN: 5764

European-Non Finnish (NFE) AF: 0.0489 AC: 54301 AN: 1111290

Other (OTH) AF: 0.0486 AC: 2931 AN: 60324

GnomAD4 genome AF: 0.0475 AC: 7233 AN: 152256 Hom.: 196 Cov.: 33 AF XY: 0.0469 AC XY: 3494 AN XY: 74450

African (AFR) AF: 0.0506 AC: 2103 AN: 41556

American (AMR) AF: 0.0391 AC: 598 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0784 AC: 272 AN: 3468

East Asian (EAS) AF: 0.0311 AC: 161 AN: 5170

South Asian (SAS) AF: 0.0245 AC: 118 AN: 4826

European-Finnish (FIN) AF: 0.0470 AC: 499 AN: 10622

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0491 AC: 3337 AN: 68004

Other (OTH) AF: 0.0564 AC: 119 AN: 2110

Alfa AF: 0.0502 Hom.: 97

Bravo AF: 0.0470

Asia WGS AF: 0.0420 AC: 146 AN: 3478

EpiCase AF: 0.0509

EpiControl AF: 0.0535

ClinVar

ClinVar submissions

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
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.49
DANN	Benign	0.78
PhyloP100		-2.8
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00023
dbscSNV1_RF	Benign	0.016
SpliceAI score (max)		0.060		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: rs35829476; hg19: chr19-49299827;