rs291402

Variant names:

• chr2-190252480-G-A
• rs291402
• NM_014362.4:c.518-173C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-190252480-G-A
• chr2-190252480-G-C
• chr2-190252480-G-T

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.518-173C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 152,048 control chromosomes in the GnomAD database, including 8,364 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.31 (8364 hom., cov: 32)
• Consequence: HIBCH NM_014362.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.00200

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=-0.92).
• BP6: Variant 2-190252480-G-A is Benign according to our data. Variant chr2-190252480-G-A is described in ClinVar as [Benign]. Clinvar id is 1251709.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HIBCH	NM_014362.4	c.518-173C>T		intron_variant	Intron 7 of 13	ENST00000359678.10	NP_055177.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HIBCH	ENST00000359678.10	c.518-173C>T		intron_variant	Intron 7 of 13	1	NM_014362.4	ENSP00000352706.5

Frequencies

GnomAD3 genomes AF: 0.309 AC: 47014 AN: 151930 Hom.: 8327 Cov.: 32

Gnomad AFR AF: 0.464

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.454

Gnomad SAS AF: 0.247

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.321

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

GnomAD4 genome AF: 0.310 AC: 47105 AN: 152048 Hom.: 8364 Cov.: 32 AF XY: 0.305 AC XY: 22649 AN XY: 74352

Gnomad4 AFR AF: 0.465

Gnomad4 AMR AF: 0.282

Gnomad4 ASJ AF: 0.218

Gnomad4 EAS AF: 0.455

Gnomad4 SAS AF: 0.248

Gnomad4 FIN AF: 0.132

Gnomad4 NFE AF: 0.248

Gnomad4 OTH AF: 0.324

Alfa AF: 0.272 Hom.: 778

Bravo AF: 0.330

Asia WGS AF: 0.353 AC: 1222 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 12, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.8
DANN	Benign	0.38

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: rs291402; hg19: chr2-191117206;