rs4660980

Variant names:

• chr1-46933825-T-C
• rs4660980
• NM_000778.4:c.1222+121A>G

Variant summary

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

The NM_000778.4(CYP4A11):​c.1222+121A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 1,445,466 control chromosomes in the GnomAD database, including 16,746 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 0.16 (2027 hom., cov: 30)
  • Exomes 𝑓: 0.14 (14719 hom.)
• Consequence: CYP4A11 NM_000778.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.47
• Publications: 10 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.268 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.1222+121A>G		intron	N/A	NP_000769.2	Q02928-1
	CYP4A11	NM_001319155.2		c.1126+121A>G		intron	N/A	NP_001306084.1
	CYP4A11	NM_001363587.2		c.928+121A>G		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.1222+121A>G		intron	N/A	ENSP00000311095.4	Q02928-1
	CYP4A11	ENST00000371905.1	TSL:1	c.1222+121A>G		intron	N/A	ENSP00000360972.1	A0A0C4DFV7
	CYP4A11	ENST00000465874.5	TSL:2	n.*20+121A>G		intron	N/A	ENSP00000476368.1	V9GY41

Frequencies

GnomAD3 genomes AF: 0.158 AC: 23983 AN: 152042 Hom.: 2023 Cov.: 30

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.149

GnomAD4 exome AF: 0.143 AC: 185325 AN: 1293306 Hom.: 14719 AF XY: 0.147 AC XY: 92392 AN XY: 630336

African (AFR) AF: 0.210 AC: 6005 AN: 28620

American (AMR) AF: 0.140 AC: 3217 AN: 23026

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 2268 AN: 19274

East Asian (EAS) AF: 0.223 AC: 8082 AN: 36222

South Asian (SAS) AF: 0.285 AC: 18344 AN: 64274

European-Finnish (FIN) AF: 0.116 AC: 5462 AN: 47024

Middle Eastern (MID) AF: 0.165 AC: 689 AN: 4172

European-Non Finnish (NFE) AF: 0.131 AC: 133244 AN: 1017188

Other (OTH) AF: 0.150 AC: 8014 AN: 53506

GnomAD4 genome AF: 0.158 AC: 24005 AN: 152160 Hom.: 2027 Cov.: 30 AF XY: 0.160 AC XY: 11866 AN XY: 74394

African (AFR) AF: 0.202 AC: 8363 AN: 41486

American (AMR) AF: 0.136 AC: 2078 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 420 AN: 3472

East Asian (EAS) AF: 0.225 AC: 1161 AN: 5162

South Asian (SAS) AF: 0.281 AC: 1353 AN: 4816

European-Finnish (FIN) AF: 0.117 AC: 1243 AN: 10598

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.130 AC: 8856 AN: 68016

Other (OTH) AF: 0.147 AC: 311 AN: 2116

Alfa AF: 0.139 Hom.: 1710

Bravo AF: 0.157

Asia WGS AF: 0.237 AC: 822 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.041
DANN	Benign	0.47
PhyloP100		-1.5
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs4660980;

hg19: chr1-47399497;

COSMIC: COSV60222779;

COSMIC: COSV60222779;