rs7921987

Variant names:

• chr10-17598747-C-G
• rs7921987
• NM_014241.4:c.605+543G>C

Your query was ambiguous. Multiple possible variants found:

• chr10-17598747-C-G
• chr10-17598747-C-T

Variant summary

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

The NM_014241.4(HACD1):​c.605+543G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 152,016 control chromosomes in the GnomAD database, including 7,501 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 0.30 (7501 hom., cov: 32)
• Consequence: HACD1 NM_014241.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.92
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HACD1	NM_014241.4	c.605+543G>C		intron_variant	Intron 5 of 6	ENST00000361271.8	NP_055056.3
HACD1	XM_005252641.5	c.497+543G>C		intron_variant	Intron 3 of 4		XP_005252698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HACD1	ENST00000361271.8	c.605+543G>C		intron_variant	Intron 5 of 6	1	NM_014241.4	ENSP00000355308.3
HACD1	ENST00000471481.1	n.391+543G>C		intron_variant	Intron 2 of 2	3
HACD1	ENST00000498812.5	n.109-4364G>C		intron_variant	Intron 2 of 3	5		ENSP00000462868.1

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46315 AN: 151898 Hom.: 7490 Cov.: 32

Gnomad AFR AF: 0.363

Gnomad AMI AF: 0.323

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.379

Gnomad EAS AF: 0.0477

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.305

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

GnomAD4 genome AF: 0.305 AC: 46338 AN: 152016 Hom.: 7501 Cov.: 32 AF XY: 0.299 AC XY: 22194 AN XY: 74312

African (AFR) AF: 0.363 AC: 15054 AN: 41472

American (AMR) AF: 0.228 AC: 3474 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.379 AC: 1315 AN: 3468

East Asian (EAS) AF: 0.0476 AC: 247 AN: 5184

South Asian (SAS) AF: 0.173 AC: 834 AN: 4810

European-Finnish (FIN) AF: 0.297 AC: 3138 AN: 10554

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.313 AC: 21246 AN: 67946

Other (OTH) AF: 0.303 AC: 640 AN: 2114

Alfa AF: 0.160 Hom.: 295

Bravo AF: 0.305

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.17
DANN	Benign	0.61
PhyloP100		-1.9
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: rs7921987; hg19: chr10-17640746;