2-190204963-T-A

Position:

• chr2-190204963-T-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014362.4(HIBCH):​c.*154A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 652,664 control chromosomes in the GnomAD database, including 26,490 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.30 (7967 hom., cov: 32)
  • Exomes 𝑓: 0.26 (18523 hom.)
• Consequence: HIBCH NM_014362.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.539

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 2-190204963-T-A is Benign according to our data. Variant chr2-190204963-T-A is described in ClinVar as [Benign]. Clinvar id is 1250382.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HIBCH	NM_014362.4	c.*154A>T		3_prime_UTR_variant	14/14	ENST00000359678.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HIBCH	ENST00000359678.10	c.*154A>T		3_prime_UTR_variant	14/14	1	NM_014362.4	P1
HIBCH	ENST00000392332.7	c.*264A>T		3_prime_UTR_variant	13/13	1
HIBCH	ENST00000399855.2	c.*17+137A>T		intron_variant		3
HIBCH	ENST00000486981.1	n.413+137A>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46117 AN: 151942 Hom.: 7943 Cov.: 32

Gnomad AFR AF: 0.445

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.279

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.312

GnomAD4 exome AF: 0.259 AC: 129598 AN: 500602 Hom.: 18523 Cov.: 3 AF XY: 0.257 AC XY: 69427 AN XY: 270506

Gnomad4 AFR exome AF: 0.449

Gnomad4 AMR exome AF: 0.233

Gnomad4 ASJ exome AF: 0.221

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.237

Gnomad4 FIN exome AF: 0.150

Gnomad4 NFE exome AF: 0.245

Gnomad4 OTH exome AF: 0.266

GnomAD4 genome AF: 0.304 AC: 46194 AN: 152062 Hom.: 7967 Cov.: 32 AF XY: 0.299 AC XY: 22214 AN XY: 74354

Gnomad4 AFR AF: 0.445

Gnomad4 AMR AF: 0.279

Gnomad4 ASJ AF: 0.213

Gnomad4 EAS AF: 0.474

Gnomad4 SAS AF: 0.243

Gnomad4 FIN AF: 0.132

Gnomad4 NFE AF: 0.247

Gnomad4 OTH AF: 0.315

Alfa AF: 0.267 Hom.: 773

Bravo AF: 0.323

Asia WGS AF: 0.350 AC: 1216 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.3
DANN	Benign	0.53

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: rs11542; hg19: chr2-191069689;