7-27573133-T-C

Position:

• chr7-27573133-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152740.4(HIBADH):​c.485-30033A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.759 in 152,166 control chromosomes in the GnomAD database, including 44,297 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 0.76 (44297 hom., cov: 32)
• Consequence: HIBADH NM_152740.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.474

Genes affected

HIBADH (HGNC:4907): (3-hydroxyisobutyrate dehydrogenase) This gene encodes a mitochondrial 3-hydroxyisobutyrate dehydrogenase enzyme. The encoded protein plays a critical role in the catabolism of L-valine by catalyzing the oxidation of 3-hydroxyisobutyrate to methylmalonate semialdehyde. [provided by RefSeq, Nov 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.921 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HIBADH	NM_152740.4	c.485-30033A>G		intron_variant		ENST00000265395.7
HIBADH	XM_047419834.1	c.182-30033A>G		intron_variant
HIBADH	XM_047419835.1	c.182-30033A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HIBADH	ENST00000265395.7	c.485-30033A>G		intron_variant		1	NM_152740.4	P1
HIBADH	ENST00000425715.1	c.313-30033A>G		intron_variant		2
HIBADH	ENST00000428288.2	c.*204-30033A>G		intron_variant, NMD_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.759 AC: 115408 AN: 152048 Hom.: 44250 Cov.: 32

Gnomad AFR AF: 0.866

Gnomad AMI AF: 0.630

Gnomad AMR AF: 0.732

Gnomad ASJ AF: 0.803

Gnomad EAS AF: 0.944

Gnomad SAS AF: 0.709

Gnomad FIN AF: 0.705

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.697

Gnomad OTH AF: 0.761

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

GnomAD4 genome AF: 0.759 AC: 115511 AN: 152166 Hom.: 44297 Cov.: 32 AF XY: 0.757 AC XY: 56332 AN XY: 74370

Gnomad4 AFR AF: 0.867

Gnomad4 AMR AF: 0.733

Gnomad4 ASJ AF: 0.803

Gnomad4 EAS AF: 0.944

Gnomad4 SAS AF: 0.708

Gnomad4 FIN AF: 0.705

Gnomad4 NFE AF: 0.697

Gnomad4 OTH AF: 0.762

Alfa AF: 0.712 Hom.: 4893

Bravo AF: 0.772

Asia WGS AF: 0.839 AC: 2918 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.32

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: rs986706; hg19: chr7-27612752;