1-46940506-G-A

Variant names:

• chr1-46940506-G-A
• rs9332982
• NM_000778.4:c.195+733C>T

Variant summary

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

The NM_000778.4(CYP4A11):​c.195+733C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0904 in 152,132 control chromosomes in the GnomAD database, including 730 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 0.090 (730 hom., cov: 32)
• Consequence: CYP4A11 NM_000778.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.549
• Publications: 4 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP4A11	NM_000778.4	c.195+733C>T		intron_variant	Intron 1 of 11	ENST00000310638.9	NP_000769.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP4A11	ENST00000310638.9	c.195+733C>T		intron_variant	Intron 1 of 11	1	NM_000778.4	ENSP00000311095.4
CYP4A11	ENST00000465874.5	n.195+733C>T		intron_variant	Intron 1 of 7	2		ENSP00000476368.1

Frequencies

GnomAD3 genomes AF: 0.0904 AC: 13738 AN: 152014 Hom.: 725 Cov.: 32

Gnomad AFR AF: 0.0649

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.0877

Gnomad FIN AF: 0.0937

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0848

Gnomad OTH AF: 0.0983

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

GnomAD4 genome AF: 0.0904 AC: 13752 AN: 152132 Hom.: 730 Cov.: 32 AF XY: 0.0935 AC XY: 6953 AN XY: 74376

African (AFR) AF: 0.0651 AC: 2704 AN: 41528

American (AMR) AF: 0.146 AC: 2239 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 364 AN: 3472

East Asian (EAS) AF: 0.194 AC: 994 AN: 5128

South Asian (SAS) AF: 0.0884 AC: 426 AN: 4820

European-Finnish (FIN) AF: 0.0937 AC: 993 AN: 10598

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

European-Non Finnish (NFE) AF: 0.0848 AC: 5765 AN: 67986

Other (OTH) AF: 0.0949 AC: 200 AN: 2108

Alfa AF: 0.0892 Hom.: 863

Bravo AF: 0.0909

Asia WGS AF: 0.128 AC: 447 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.75
DANN	Benign	0.45
PhyloP100		-0.55
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: rs9332982; hg19: chr1-47406178;