rs2252808

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
• Publications: 4 publications found

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]

HACD1 Gene-Disease associations (from GenCC):

• congenital myopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• congenital myopathy 11

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
• congenital fiber-type disproportion myopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014241.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HACD1	NM_014241.4	MANE Select	c.376-71G>A		intron	N/A	NP_055056.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HACD1	ENST00000361271.8	TSL:1 MANE Select	c.376-71G>A		intron	N/A	ENSP00000355308.3	B0YJ81-1
	HACD1	ENST00000632169.1	TSL:1	n.525G>A		non_coding_transcript_exon	Exon 2 of 2
	HACD1	ENST00000957763.1		c.466-71G>A		intron	N/A	ENSP00000627822.1

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

African (AFR) AF: 0.765 AC: 23219 AN: 30342

American (AMR) AF: 0.609 AC: 25333 AN: 41592

Ashkenazi Jewish (ASJ) AF: 0.589 AC: 14711 AN: 24972

East Asian (EAS) AF: 0.545 AC: 21248 AN: 39002

South Asian (SAS) AF: 0.459 AC: 37475 AN: 81634

European-Finnish (FIN) AF: 0.539 AC: 28581 AN: 53010

Middle Eastern (MID) AF: 0.620 AC: 3410 AN: 5502

European-Non Finnish (NFE) AF: 0.563 AC: 573809 AN: 1019144

Other (OTH) 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

African (AFR) AF: 0.754 AC: 31264 AN: 41460

American (AMR) AF: 0.584 AC: 8906 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.596 AC: 2067 AN: 3470

East Asian (EAS) AF: 0.518 AC: 2676 AN: 5166

South Asian (SAS) AF: 0.465 AC: 2240 AN: 4814

European-Finnish (FIN) AF: 0.537 AC: 5657 AN: 10534

Middle Eastern (MID) AF: 0.612 AC: 180 AN: 294

European-Non Finnish (NFE) AF: 0.566 AC: 38504 AN: 67978

Other (OTH) AF: 0.616 AC: 1302 AN: 2112

Alfa AF: 0.614 Hom.: 5111

Bravo AF: 0.628

Asia WGS AF: 0.515 AC: 1790 AN: 3474

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.31
DANN	Benign	0.32
PhyloP100		-0.16
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: rs2252808; hg19: chr10-17645814; COSMIC: COSV63516471; COSMIC: COSV63516471;