rs1456114

Positions:

• chr3-123526305-G-A

Variant summary

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

The NM_198402.5(HACD2):​c.381+2081C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.545 in 152,096 control chromosomes in the GnomAD database, including 25,327 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 0.55 (25327 hom., cov: 32)
• Consequence: HACD2 NM_198402.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.88

Genes affected

HACD2 (HGNC:9640): (3-hydroxyacyl-CoA dehydratase 2) The protein encoded by this gene can catalyze the third step (dehydration) in the conversion of long chain fatty acids to very long chain fatty acids. The encoded protein localizes to the endoplasmic reticulum membrane. [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.681 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HACD2	NM_198402.5	c.381+2081C>T		intron_variant		ENST00000383657.10	NP_940684.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HACD2	ENST00000383657.10	c.381+2081C>T		intron_variant		1	NM_198402.5	ENSP00000373153.5
HACD2	ENST00000469317.1	c.48+2081C>T		intron_variant		3		ENSP00000419237.1

Frequencies

GnomAD3 genomes AF: 0.545 AC: 82892 AN: 151978 Hom.: 25332 Cov.: 32

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.618

Gnomad AMR AF: 0.530

Gnomad ASJ AF: 0.655

Gnomad EAS AF: 0.357

Gnomad SAS AF: 0.609

Gnomad FIN AF: 0.764

Gnomad MID AF: 0.599

Gnomad NFE AF: 0.686

Gnomad OTH AF: 0.575

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

GnomAD4 genome AF: 0.545 AC: 82918 AN: 152096 Hom.: 25327 Cov.: 32 AF XY: 0.548 AC XY: 40745 AN XY: 74362

Gnomad4 AFR AF: 0.268

Gnomad4 AMR AF: 0.530

Gnomad4 ASJ AF: 0.655

Gnomad4 EAS AF: 0.356

Gnomad4 SAS AF: 0.608

Gnomad4 FIN AF: 0.764

Gnomad4 NFE AF: 0.686

Gnomad4 OTH AF: 0.574

Alfa AF: 0.606 Hom.: 5052

Bravo AF: 0.512

Asia WGS AF: 0.484 AC: 1680 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.064
DANN	Benign	0.82

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: rs1456114; hg19: chr3-123245152;