chr10-17603815-C-T

Variant names:

• chr10-17603815-C-T
• rs2252808
• NM_014241.4:c.376-71G>A

Variant summary

Our verdict is Benign. The variant received -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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
HACD1	NM_014241.4	c.376-71G>A		intron_variant	Intron 2 of 6	ENST00000361271.8	NP_055056.3
HACD1	XM_005252641.5	c.375+115G>A		intron_variant	Intron 2 of 4		XP_005252698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HACD1	ENST00000361271.8	c.376-71G>A		intron_variant	Intron 2 of 6	1	NM_014241.4	ENSP00000355308.3

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 AC: 23219 AN: 30342

Gnomad4 AMR exome AF: 0.609 AC: 25333 AN: 41592

Gnomad4 ASJ exome AF: 0.589 AC: 14711 AN: 24972

Gnomad4 EAS exome AF: 0.545 AC: 21248 AN: 39002

Gnomad4 SAS exome AF: 0.459 AC: 37475 AN: 81634

Gnomad4 FIN exome AF: 0.539 AC: 28581 AN: 53010

Gnomad4 NFE exome AF: 0.563 AC: 573809 AN: 1019144

Gnomad4 Remaining exome AF: 0.565 AC: 31938 AN: 56552

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 AC: 0.754076 AN: 0.754076

Gnomad4 AMR AF: 0.584 AC: 0.583847 AN: 0.583847

Gnomad4 ASJ AF: 0.596 AC: 0.595677 AN: 0.595677

Gnomad4 EAS AF: 0.518 AC: 0.518002 AN: 0.518002

Gnomad4 SAS AF: 0.465 AC: 0.46531 AN: 0.46531

Gnomad4 FIN AF: 0.537 AC: 0.537023 AN: 0.537023

Gnomad4 NFE AF: 0.566 AC: 0.566419 AN: 0.566419

Gnomad4 OTH AF: 0.616 AC: 0.616477 AN: 0.616477

Alfa AF: 0.614 Hom.: 5111

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

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

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