rs11789272

Positions:

• chr9-21030852-G-A
• chr9-21030852-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001010915.5(HACD4):​c.38+701C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 152,084 control chromosomes in the GnomAD database, including 7,600 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 0.31 (7600 hom., cov: 32)
• Consequence: HACD4 NM_001010915.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.478

Genes affected

HACD4 (HGNC:20920): (3-hydroxyacyl-CoA dehydratase 4) Enables 3-hydroxyacyl-CoA dehydratase activity and enzyme binding activity. Involved in fatty acid elongation and very long-chain fatty acid biosynthetic process. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.526 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HACD4	NM_001010915.5	c.38+701C>T		intron_variant		ENST00000495827.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HACD4	ENST00000495827.3	c.38+701C>T		intron_variant		2	NM_001010915.5	P1

Frequencies

GnomAD3 genomes AF: 0.306 AC: 46556 AN: 151968 Hom.: 7596 Cov.: 32

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.414

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.542

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.366

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.295

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

GnomAD4 genome AF: 0.306 AC: 46574 AN: 152084 Hom.: 7600 Cov.: 32 AF XY: 0.317 AC XY: 23577 AN XY: 74328

Gnomad4 AFR AF: 0.309

Gnomad4 AMR AF: 0.414

Gnomad4 ASJ AF: 0.221

Gnomad4 EAS AF: 0.542

Gnomad4 SAS AF: 0.292

Gnomad4 FIN AF: 0.366

Gnomad4 NFE AF: 0.261

Gnomad4 OTH AF: 0.295

Alfa AF: 0.278 Hom.: 1271

Bravo AF: 0.309

Asia WGS AF: 0.369 AC: 1284 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	15
DANN	Benign	0.89

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: rs11789272; hg19: chr9-21030851; COSMIC: COSV72136671; COSMIC: COSV72136671;