rs1456114

Variant names:

• chr3-123526305-G-A
• rs1456114
• NM_198402.5:c.381+2081C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
HACD2	NM_198402.5	c.381+2081C>T		intron_variant	Intron 4 of 6	ENST00000383657.10	NP_940684.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HACD2	ENST00000383657.10	c.381+2081C>T		intron_variant	Intron 4 of 6	1	NM_198402.5	ENSP00000373153.5
HACD2	ENST00000469317.1	c.48+2081C>T		intron_variant	Intron 4 of 5	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

African (AFR) AF: 0.268 AC: 11101 AN: 41464

American (AMR) AF: 0.530 AC: 8099 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.655 AC: 2271 AN: 3466

East Asian (EAS) AF: 0.356 AC: 1842 AN: 5174

South Asian (SAS) AF: 0.608 AC: 2927 AN: 4816

European-Finnish (FIN) AF: 0.764 AC: 8079 AN: 10580

Middle Eastern (MID) AF: 0.610 AC: 178 AN: 292

European-Non Finnish (NFE) AF: 0.686 AC: 46648 AN: 67994

Other (OTH) AF: 0.574 AC: 1212 AN: 2112

Alfa AF: 0.596 Hom.: 5079

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
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1456114; hg19: chr3-123245152;