rs10486552

chr7-27648702-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_152740.4(HIBADH):c.252+771A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00855 in 152,332 control chromosomes in the GnomAD database, including 12 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 0.0086 (12 hom., cov: 33)
• Consequence: HIBADH NM_152740.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.607

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]

LOC105375211 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00855 (1303/152332) while in subpopulation SAS AF= 0.0301 (145/4824). AF 95% confidence interval is 0.0261. There are 12 homozygotes in gnomad4. There are 627 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HIBADH	NM_152740.4	c.252+771A>G		intron_variant		ENST00000265395.7
LOC105375211	XR_007060268.1	n.85+772T>C		intron_variant, non_coding_transcript_variant
LOC105375211	XR_927139.3	n.85+772T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HIBADH	ENST00000265395.7	c.252+771A>G		intron_variant		1	NM_152740.4	P1
HIBADH	ENST00000428288.2	c.91+13996A>G		intron_variant, NMD_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.00855 AC: 1302 AN: 152214 Hom.: 12 Cov.: 33

Gnomad AFR AF: 0.00261

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0141

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00423

Gnomad SAS AF: 0.0298

Gnomad FIN AF: 0.00254

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0113

Gnomad OTH AF: 0.00623

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

GnomAD4 genome AF: 0.00855 AC: 1303 AN: 152332 Hom.: 12 Cov.: 33 AF XY: 0.00842 AC XY: 627 AN XY: 74480

Gnomad4 AFR AF: 0.00260

Gnomad4 AMR AF: 0.0140

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00424

Gnomad4 SAS AF: 0.0301

Gnomad4 FIN AF: 0.00254

Gnomad4 NFE AF: 0.0113

Gnomad4 OTH AF: 0.00616

Alfa AF: 0.00948 Hom.: 1

Bravo AF: 0.00960

Asia WGS AF: 0.0190 AC: 66 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.84
Dann	Benign	0.37

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: rs10486552; hg19: chr7-27688321;