rs2252808

Positions:

• chr10-17603815-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014241.4(HACD1):​c.376-71G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.567 in 1,503,736 control chromosomes in the GnomAD database, including 244,929 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.61 (29263 hom., cov: 31)
  • Exomes 𝑓: 0.56 (215666 hom.)
• Consequence: HACD1 NM_014241.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.156

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 10-17603815-C-T is Benign according to our data. Variant chr10-17603815-C-T is described in ClinVar as [Benign]. Clinvar id is 1228253.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.747 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HACD1	NM_014241.4	c.376-71G>A		intron_variant		ENST00000361271.8	NP_055056.3
HACD1	XM_005252641.5	c.375+115G>A		intron_variant			XP_005252698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HACD1	ENST00000361271.8	c.376-71G>A		intron_variant		1	NM_014241.4	ENSP00000355308	P1
HACD1	ENST00000632169.1	n.525G>A		non_coding_transcript_exon_variant	2/2	1
HACD1	ENST00000466335.1	c.272-71G>A		intron_variant		2		ENSP00000462336
HACD1	ENST00000471481.1	n.14G>A		non_coding_transcript_exon_variant	1/3	3

Frequencies

GnomAD3 genomes AF: 0.614 AC: 93179 AN: 151868 Hom.: 29202 Cov.: 31

Gnomad AFR AF: 0.754

Gnomad AMI AF: 0.562

Gnomad AMR AF: 0.584

Gnomad ASJ AF: 0.596

Gnomad EAS AF: 0.518

Gnomad SAS AF: 0.465

Gnomad FIN AF: 0.537

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.566

Gnomad OTH AF: 0.612

GnomAD4 exome AF: 0.562 AC: 759724 AN: 1351750 Hom.: 215666 Cov.: 22 AF XY: 0.558 AC XY: 378101 AN XY: 677310

Gnomad4 AFR exome AF: 0.765

Gnomad4 AMR exome AF: 0.609

Gnomad4 ASJ exome AF: 0.589

Gnomad4 EAS exome AF: 0.545

Gnomad4 SAS exome AF: 0.459

Gnomad4 FIN exome AF: 0.539

Gnomad4 NFE exome AF: 0.563

Gnomad4 OTH exome AF: 0.565

GnomAD4 genome AF: 0.614 AC: 93304 AN: 151986 Hom.: 29263 Cov.: 31 AF XY: 0.607 AC XY: 45110 AN XY: 74258

Gnomad4 AFR AF: 0.754

Gnomad4 AMR AF: 0.584

Gnomad4 ASJ AF: 0.596

Gnomad4 EAS AF: 0.518

Gnomad4 SAS AF: 0.465

Gnomad4 FIN AF: 0.537

Gnomad4 NFE AF: 0.566

Gnomad4 OTH AF: 0.616

Alfa AF: 0.610 Hom.: 4884

Bravo AF: 0.628

Asia WGS AF: 0.515 AC: 1790 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.31
DANN	Benign	0.32

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: rs2252808; hg19: chr10-17645814; COSMIC: COSV63516471; COSMIC: COSV63516471;