10-17613982-T-C

Variant summary

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

The NM_014241.4(HACD1):c.257+3101A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.817 in 152,192 control chromosomes in the GnomAD database, including 51,486 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 0.82 (51486 hom., cov: 33)
• Consequence: HACD1 NM_014241.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.558

Genes affected

HACD1 (HGNC:9639): (3-hydroxyacyl-CoA dehydratase 1) The protein encoded by this gene contains a characteristic catalytic motif of the protein tyrosine phosphatases (PTPs) family. The PTP motif of this protein has the highly conserved arginine residue replaced by a proline residue; thus it may represent a distinct class of PTPs. Members of the PTP family are known to be signaling molecules that regulate a variety of cellular processes. This gene was preferentially expressed in both adult and fetal heart. A much lower expression level was detected in skeletal and smooth muscle tissues, and no expression was observed in other tissues. The tissue specific expression in the developing and adult heart suggests a role in regulating cardiac development and differentiation. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.946 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HACD1	NM_014241.4	c.257+3101A>G		intron_variant		ENST00000361271.8
HACD1	XM_005252641.5	c.257+3101A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HACD1	ENST00000361271.8	c.257+3101A>G		intron_variant		1	NM_014241.4	P1
HACD1	ENST00000632169.1	n.292+3101A>G		intron_variant, non_coding_transcript_variant		1
HACD1	ENST00000466335.1	c.153+3101A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.816 AC: 124158 AN: 152074 Hom.: 51421 Cov.: 33

Gnomad AFR AF: 0.954

Gnomad AMI AF: 0.715

Gnomad AMR AF: 0.830

Gnomad ASJ AF: 0.842

Gnomad EAS AF: 0.895

Gnomad SAS AF: 0.791

Gnomad FIN AF: 0.738

Gnomad MID AF: 0.829

Gnomad NFE AF: 0.738

Gnomad OTH AF: 0.819

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

GnomAD4 genome AF: 0.817 AC: 124286 AN: 152192 Hom.: 51486 Cov.: 33 AF XY: 0.817 AC XY: 60750 AN XY: 74390

Gnomad4 AFR AF: 0.954

Gnomad4 AMR AF: 0.830

Gnomad4 ASJ AF: 0.842

Gnomad4 EAS AF: 0.895

Gnomad4 SAS AF: 0.791

Gnomad4 FIN AF: 0.738

Gnomad4 NFE AF: 0.738

Gnomad4 OTH AF: 0.823

Alfa AF: 0.758 Hom.: 57690

Bravo AF: 0.831

Asia WGS AF: 0.866 AC: 3013 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	1.5
Dann	Benign	0.55

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: rs2461891; hg19: chr10-17655981;