19-41398260-C-T

Variant names:

• chr19-41398260-C-T
• rs3810174
• NM_000709.4:c.108+325C>T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000709.4(BCKDHA):​c.108+325C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.62 in 151,874 control chromosomes in the GnomAD database, including 29,646 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.62 (29646 hom., cov: 30)
• Consequence: BCKDHA NM_000709.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.482

Genes affected

BCKDHA (HGNC:986): (branched chain keto acid dehydrogenase E1 subunit alpha) The branched-chain alpha-keto acid (BCAA) dehydrogenase (BCKD) complex is an innter mitochondrial enzyme complex that catalyzes the second major step in the catabolism of the branched-chain amino acids leucine, isoleucine, and valine. The BCKD complex consists of three catalytic components: a heterotetrameric (alpha2-beta2) branched-chain alpha-keto acid decarboxylase (E1), a dihydrolipoyl transacylase (E2), and a dihydrolipoamide dehydrogenase (E3). This gene encodes the alpha subunit of the decarboxylase (E1) component. Mutations in this gene result in maple syrup urine disease, type IA. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Sep 2009]

ENSG00000255730 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 19-41398260-C-T is Benign according to our data. Variant chr19-41398260-C-T is described in ClinVar as [Benign]. Clinvar id is 680490.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.696 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCKDHA	NM_000709.4	c.108+325C>T		intron_variant	Intron 1 of 8	ENST00000269980.7	NP_000700.1
BCKDHA	NM_001164783.2	c.108+325C>T		intron_variant	Intron 1 of 8		NP_001158255.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCKDHA	ENST00000269980.7	c.108+325C>T		intron_variant	Intron 1 of 8	1	NM_000709.4	ENSP00000269980.2
ENSG00000255730	ENST00000540732.3	c.211-12377C>T		intron_variant	Intron 2 of 9	2		ENSP00000443246.1

Frequencies

GnomAD3 genomes AF: 0.620 AC: 94078 AN: 151758 Hom.: 29625 Cov.: 30

Gnomad AFR AF: 0.703

Gnomad AMI AF: 0.770

Gnomad AMR AF: 0.544

Gnomad ASJ AF: 0.621

Gnomad EAS AF: 0.428

Gnomad SAS AF: 0.590

Gnomad FIN AF: 0.660

Gnomad MID AF: 0.618

Gnomad NFE AF: 0.595

Gnomad OTH AF: 0.607

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

GnomAD4 genome AF: 0.620 AC: 94144 AN: 151874 Hom.: 29646 Cov.: 30 AF XY: 0.618 AC XY: 45870 AN XY: 74204

Gnomad4 AFR AF: 0.703

Gnomad4 AMR AF: 0.543

Gnomad4 ASJ AF: 0.621

Gnomad4 EAS AF: 0.429

Gnomad4 SAS AF: 0.589

Gnomad4 FIN AF: 0.660

Gnomad4 NFE AF: 0.595

Gnomad4 OTH AF: 0.608

Alfa AF: 0.599 Hom.: 15135

Bravo AF: 0.615

Asia WGS AF: 0.525 AC: 1826 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 19, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.6
DANN	Benign	0.61

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: rs3810174; hg19: chr19-41904165;