rs221330

Positions:

• chr4-108000211-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005327.7(HADH):​c.133-9548G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 152,162 control chromosomes in the GnomAD database, including 5,315 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 0.25 (5315 hom., cov: 32)
• Consequence: HADH NM_005327.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.290

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HADH	NM_005327.7	c.133-9548G>A		intron_variant		ENST00000309522.8	NP_005318.6
HADH	NM_001184705.4	c.133-9548G>A		intron_variant			NP_001171634.3
HADH	XR_007096395.1	n.177-9548G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HADH	ENST00000309522.8	c.133-9548G>A		intron_variant		1	NM_005327.7	ENSP00000312288	P4

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37705 AN: 152044 Hom.: 5308 Cov.: 32

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.342

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.336

Gnomad SAS AF: 0.381

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.330

Gnomad NFE AF: 0.304

Gnomad OTH AF: 0.268

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

GnomAD4 genome AF: 0.248 AC: 37722 AN: 152162 Hom.: 5315 Cov.: 32 AF XY: 0.246 AC XY: 18315 AN XY: 74382

Gnomad4 AFR AF: 0.118

Gnomad4 AMR AF: 0.255

Gnomad4 ASJ AF: 0.369

Gnomad4 EAS AF: 0.337

Gnomad4 SAS AF: 0.381

Gnomad4 FIN AF: 0.227

Gnomad4 NFE AF: 0.304

Gnomad4 OTH AF: 0.275

Alfa AF: 0.299 Hom.: 11496

Bravo AF: 0.242

Asia WGS AF: 0.372 AC: 1295 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.87
DANN	Benign	0.41

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: rs221330; hg19: chr4-108921367;