9-21030852-G-A

Variant names:

• chr9-21030852-G-A
• rs11789272
• NM_001010915.5:c.38+701C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001010915.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HACD4	NM_001010915.5	MANE Select	c.38+701C>T		intron	N/A	NP_001010915.2
	HACD4	NM_001321903.2		c.38+701C>T		intron	N/A	NP_001308832.1
	HACD4	NM_001321883.2		c.-74+548C>T		intron	N/A	NP_001308812.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HACD4	ENST00000495827.3	TSL:2 MANE Select	c.38+701C>T		intron	N/A	ENSP00000419503.1

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

African (AFR) AF: 0.309 AC: 12827 AN: 41458

American (AMR) AF: 0.414 AC: 6329 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 766 AN: 3470

East Asian (EAS) AF: 0.542 AC: 2801 AN: 5164

South Asian (SAS) AF: 0.292 AC: 1409 AN: 4820

European-Finnish (FIN) AF: 0.366 AC: 3862 AN: 10566

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.261 AC: 17733 AN: 67996

Other (OTH) AF: 0.295 AC: 622 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	15
DANN	Benign	0.89
PhyloP100		0.48
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: rs11789272; hg19: chr9-21030851; COSMIC: COSV72136671; COSMIC: COSV72136671;