4-108014612-CTTTT-CTTTTT

Position:

• chr4-108014612-CTTTT-CTTTTT

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BS1

The ENST00000309522.8(HADH):​c.419+39dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00173 in 1,268,284 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000021 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0020 (0 hom.)
• Consequence: HADH ENST00000309522.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11

Genes affected

HADH (HGNC:4799): (hydroxyacyl-CoA dehydrogenase) This gene is a member of the 3-hydroxyacyl-CoA dehydrogenase gene family. The encoded protein functions in the mitochondrial matrix to catalyze the oxidation of straight-chain 3-hydroxyacyl-CoAs as part of the beta-oxidation pathway. Its enzymatic activity is highest with medium-chain-length fatty acids. Mutations in this gene cause one form of familial hyperinsulinemic hypoglycemia. The human genome contains a related pseudogene of this gene on chromosome 15. [provided by RefSeq, May 2010]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS1: Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.00195 (2190/1122402) while in subpopulation AFR AF= 0.00939 (237/25246). AF 95% confidence interval is 0.00841. There are 0 homozygotes in gnomad4_exome. There are 1000 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HADH	NM_005327.7	c.419+39dup		intron_variant		ENST00000309522.8	NP_005318.6
HADH	NM_001184705.4	c.419+39dup		intron_variant			NP_001171634.3
HADH	NM_001331027.2	c.431+39dup		intron_variant			NP_001317956.2
HADH	XR_007096395.1	n.463+39dup		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HADH	ENST00000309522.8	c.419+39dup		intron_variant		1	NM_005327.7	ENSP00000312288	P4

Frequencies

GnomAD3 genomes AF: 0.0000206 AC: 3 AN: 145882 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000510

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000151

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00195 AC: 2190 AN: 1122402 Hom.: 0 Cov.: 0 AF XY: 0.00178 AC XY: 1000 AN XY: 562640

Gnomad4 AFR exome AF: 0.00939

Gnomad4 AMR exome AF: 0.000142

Gnomad4 ASJ exome AF: 0.000329

Gnomad4 EAS exome AF: 0.000278

Gnomad4 SAS exome AF: 0.000974

Gnomad4 FIN exome AF: 0.000186

Gnomad4 NFE exome AF: 0.00208

Gnomad4 OTH exome AF: 0.00209

GnomAD4 genome AF: 0.0000206 AC: 3 AN: 145882 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 70800

Gnomad4 AFR AF: 0.0000510

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000151

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs550348868; hg19: chr4-108935768;