2-190205356-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_014362.4(HIBCH):c.1046-124T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00207 in 640,846 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0063 (9 hom., cov: 32)
  • Exomes 𝑓: 0.00077 (1 hom.)
• Consequence: HIBCH NM_014362.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.18

Genes affected

HIBCH (HGNC:4908): (3-hydroxyisobutyryl-CoA hydrolase) This gene encodes the enzyme responsible for hydrolysis of both HIBYL-CoA and beta-hydroxypropionyl-CoA. Mutations in this gene have been associated with 3-hyroxyisobutyryl-CoA hydrolase deficiency. Alternative splicing results in multiple transcript variants.[provided by RefSeq, May 2010]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 2-190205356-A-T is Benign according to our data. Variant chr2-190205356-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 1321780.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00626 (953/152218) while in subpopulation AFR AF= 0.0218 (905/41534). AF 95% confidence interval is 0.0206. There are 9 homozygotes in gnomad4. There are 446 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HIBCH	NM_014362.4	c.1046-124T>A		intron_variant		ENST00000359678.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HIBCH	ENST00000359678.10	c.1046-124T>A		intron_variant		1	NM_014362.4	P1
HIBCH	ENST00000392332.7	c.1012-124T>A		intron_variant		1
HIBCH	ENST00000410045.5	c.377-124T>A		intron_variant		3
HIBCH	ENST00000486981.1	n.281-124T>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.00627 AC: 953 AN: 152100 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.0219

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00210

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00525

GnomAD4 exome AF: 0.000765 AC: 374 AN: 488628 Hom.: 1 AF XY: 0.000604 AC XY: 159 AN XY: 263056

Gnomad4 AFR exome AF: 0.0208

Gnomad4 AMR exome AF: 0.00154

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000200

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000341

Gnomad4 OTH exome AF: 0.00204

GnomAD4 genome AF: 0.00626 AC: 953 AN: 152218 Hom.: 9 Cov.: 32 AF XY: 0.00599 AC XY: 446 AN XY: 74432

Gnomad4 AFR AF: 0.0218

Gnomad4 AMR AF: 0.00209

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.00520

Alfa AF: 0.00506 Hom.: 0

Bravo AF: 0.00716

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 12, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	4.1
Dann	Benign	0.72

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: rs189691978; hg19: chr2-191070082;