NM_000778.4:c.1461C>T

Variant names:

• chr1-46930214-G-A
• rs9333036
• NM_000778.4:c.1461C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000778.4(CYP4A11):​c.1461C>T​(p.Ile487Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00343 in 1,614,112 control chromosomes in the GnomAD database, including 126 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.017 (54 hom., cov: 30)
  • Exomes 𝑓: 0.0020 (72 hom.)
• Consequence: CYP4A11 NM_000778.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.22
• Publications: 1 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 1-46930214-G-A is Benign according to our data. Variant chr1-46930214-G-A is described in ClinVar as Benign. ClinVar VariationId is 774797.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.22 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0576 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.1461C>T	p.Ile487Ile	synonymous	Exon 12 of 12	NP_000769.2	Q02928-1
	CYP4A11	NM_001319155.2		c.1365C>T	p.Ile455Ile	synonymous	Exon 12 of 12	NP_001306084.1
	CYP4A11	NM_001363587.2		c.1167C>T	p.Ile389Ile	synonymous	Exon 10 of 10	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.1461C>T	p.Ile487Ile	synonymous	Exon 12 of 12	ENSP00000311095.4	Q02928-1
	CYP4A11	ENST00000909039.1		c.1572C>T	p.Ile524Ile	synonymous	Exon 12 of 12	ENSP00000579098.1
	CYP4A11	ENST00000909036.1		c.1485C>T	p.Ile495Ile	synonymous	Exon 12 of 12	ENSP00000579095.1

Frequencies

GnomAD3 genomes AF: 0.0171 AC: 2609 AN: 152154 Hom.: 53 Cov.: 30

Gnomad AFR AF: 0.0596

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00471

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000515

Gnomad OTH AF: 0.0158

GnomAD2 exomes AF: 0.00483 AC: 1214 AN: 251388 AF XY: 0.00351

Gnomad AFR exome AF: 0.0621

Gnomad AMR exome AF: 0.00341

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000484

Gnomad OTH exome AF: 0.00473

GnomAD4 exome AF: 0.00200 AC: 2927 AN: 1461840 Hom.: 72 Cov.: 29 AF XY: 0.00175 AC XY: 1270 AN XY: 727220

African (AFR) AF: 0.0632 AC: 2115 AN: 33478

American (AMR) AF: 0.00398 AC: 178 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0000765 AC: 2 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000128 AC: 11 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00468 AC: 27 AN: 5764

European-Non Finnish (NFE) AF: 0.000295 AC: 328 AN: 1111980

Other (OTH) AF: 0.00440 AC: 266 AN: 60394

GnomAD4 genome AF: 0.0172 AC: 2616 AN: 152272 Hom.: 54 Cov.: 30 AF XY: 0.0166 AC XY: 1237 AN XY: 74458

African (AFR) AF: 0.0595 AC: 2474 AN: 41546

American (AMR) AF: 0.00470 AC: 72 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000515 AC: 35 AN: 68016

Other (OTH) AF: 0.0156 AC: 33 AN: 2110

Alfa AF: 0.00520 Hom.: 4

Bravo AF: 0.0196

Asia WGS AF: 0.00375 AC: 14 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000237

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.8
DANN	Benign	0.66
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism

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: rs9333036; hg19: chr1-47395886;