rs9333025

Variant names:

• chr1-46931231-C-T
• rs9333025
• NM_000778.4:c.1365-921G>A

Variant summary

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

The NM_000778.4(CYP4A11):​c.1365-921G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.096 in 152,222 control chromosomes in the GnomAD database, including 797 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 0.096 (797 hom., cov: 32)
• Consequence: CYP4A11 NM_000778.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.635
• Publications: 22 publications found

Genes affected

CYP4A11 (HGNC:2642): (cytochrome P450 family 4 subfamily A member 11) This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum and hydroxylates medium-chain fatty acids such as laurate and myristate. Multiple transcript variants have been found for this gene. [provided by RefSeq, Jan 2016]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000778.4. 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
	CYP4A11	NM_000778.4	MANE Select	c.1365-921G>A		intron	N/A	NP_000769.2	Q02928-1
	CYP4A11	NM_001319155.2		c.1269-921G>A		intron	N/A	NP_001306084.1
	CYP4A11	NM_001363587.2		c.1071-921G>A		intron	N/A	NP_001350516.1	V9GZ77

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP4A11	ENST00000310638.9	TSL:1 MANE Select	c.1365-921G>A		intron	N/A	ENSP00000311095.4	Q02928-1
	CYP4A11	ENST00000909039.1		c.1476-921G>A		intron	N/A	ENSP00000579098.1
	CYP4A11	ENST00000909036.1		c.1389-921G>A		intron	N/A	ENSP00000579095.1

Frequencies

GnomAD3 genomes AF: 0.0959 AC: 14586 AN: 152104 Hom.: 792 Cov.: 32

Gnomad AFR AF: 0.0839

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.0870

Gnomad FIN AF: 0.0938

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0848

Gnomad OTH AF: 0.101

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

GnomAD4 genome AF: 0.0960 AC: 14606 AN: 152222 Hom.: 797 Cov.: 32 AF XY: 0.0986 AC XY: 7337 AN XY: 74436

African (AFR) AF: 0.0841 AC: 3494 AN: 41528

American (AMR) AF: 0.148 AC: 2267 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 383 AN: 3470

East Asian (EAS) AF: 0.194 AC: 1003 AN: 5160

South Asian (SAS) AF: 0.0877 AC: 423 AN: 4826

European-Finnish (FIN) AF: 0.0938 AC: 995 AN: 10612

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0848 AC: 5768 AN: 68018

Other (OTH) AF: 0.0976 AC: 206 AN: 2110

Alfa AF: 0.0903 Hom.: 840

Bravo AF: 0.0973

Asia WGS AF: 0.131 AC: 457 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.1
DANN	Benign	0.54
PhyloP100		0.64
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: rs9333025; hg19: chr1-47396903;