rs7918263

Variant names:

• chr10-17615153-A-T
• rs7918263
• NM_014241.4:c.257+1930T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014241.4(HACD1):​c.257+1930T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 152,156 control chromosomes in the GnomAD database, including 13,556 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 0.41 (13556 hom., cov: 34)
• Consequence: HACD1 NM_014241.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.204
• Publications: 1 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.514 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HACD1	NM_014241.4	c.257+1930T>A		intron_variant	Intron 1 of 6	ENST00000361271.8	NP_055056.3
HACD1	XM_005252641.5	c.257+1930T>A		intron_variant	Intron 1 of 4		XP_005252698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HACD1	ENST00000361271.8	c.257+1930T>A		intron_variant	Intron 1 of 6	1	NM_014241.4	ENSP00000355308.3
HACD1	ENST00000632169.1	n.292+1930T>A		intron_variant	Intron 1 of 1	1
HACD1	ENST00000466335.1	c.152+1930T>A		intron_variant	Intron 1 of 4	2		ENSP00000462336.1

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62945 AN: 152038 Hom.: 13547 Cov.: 34

Gnomad AFR AF: 0.520

Gnomad AMI AF: 0.429

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.358

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.351

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.413

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

GnomAD4 genome AF: 0.414 AC: 62993 AN: 152156 Hom.: 13556 Cov.: 34 AF XY: 0.407 AC XY: 30309 AN XY: 74394

African (AFR) AF: 0.520 AC: 21578 AN: 41510

American (AMR) AF: 0.406 AC: 6202 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.358 AC: 1242 AN: 3472

East Asian (EAS) AF: 0.165 AC: 855 AN: 5176

South Asian (SAS) AF: 0.281 AC: 1354 AN: 4826

European-Finnish (FIN) AF: 0.351 AC: 3708 AN: 10572

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.392 AC: 26670 AN: 67996

Other (OTH) AF: 0.411 AC: 868 AN: 2110

Alfa AF: 0.403 Hom.: 1583

Bravo AF: 0.428

Asia WGS AF: 0.223 AC: 779 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	3.4
DANN	Benign	0.66
PhyloP100		-0.20
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: rs7918263; hg19: chr10-17657152;