rs10486552

Variant names:

• chr7-27648702-T-C
• rs10486552
• NM_152740.4:c.252+771A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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]

HIBADH Gene-Disease associations (from GenCC):

• 3-hydroxyisobutyric aciduria

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen
• inborn organic aciduria

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

LOC105375211 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HIBADH	NM_152740.4	c.252+771A>G		intron_variant	Intron 2 of 7	ENST00000265395.7	NP_689953.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HIBADH	ENST00000265395.7	c.252+771A>G		intron_variant	Intron 2 of 7	1	NM_152740.4	ENSP00000265395.2
HIBADH	ENST00000428288.2	n.91+13996A>G		intron_variant	Intron 1 of 6	3		ENSP00000393365.1

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

African (AFR) AF: 0.00260 AC: 108 AN: 41570

American (AMR) AF: 0.0140 AC: 215 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00424 AC: 22 AN: 5184

South Asian (SAS) AF: 0.0301 AC: 145 AN: 4824

European-Finnish (FIN) AF: 0.00254 AC: 27 AN: 10624

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0113 AC: 770 AN: 68036

Other (OTH) AF: 0.00616 AC: 13 AN: 2110

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
PhyloP100		-0.61
Mutation Taster		=100/0	polymorphism

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: rs10486552; hg19: chr7-27688321;