1-46938514-T-C

Variant names:

• chr1-46938514-T-C
• rs9332998
• NM_000778.4:c.196-377A>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.196-377A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 152,256 control chromosomes in the GnomAD database, including 2,010 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 (2010 hom., cov: 33)
• Consequence: CYP4A11 NM_000778.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.504
• Publications: 21 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=-0.85).
• 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP4A11	NM_000778.4	MANE Select	c.196-377A>G		intron	N/A	NP_000769.2
	CYP4A11	NM_001319155.2		c.196-377A>G		intron	N/A	NP_001306084.1
	CYP4A11	NM_001363587.2		c.196-377A>G		intron	N/A	NP_001350516.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP4A11	ENST00000310638.9	TSL:1 MANE Select	c.196-377A>G		intron	N/A	ENSP00000311095.4
	CYP4A11	ENST00000371905.1	TSL:1	c.196-377A>G		intron	N/A	ENSP00000360972.1
	CYP4A11	ENST00000465874.5	TSL:2	n.196-377A>G		intron	N/A	ENSP00000476368.1

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23908 AN: 152138 Hom.: 2007 Cov.: 33

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.150

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

GnomAD4 genome AF: 0.157 AC: 23925 AN: 152256 Hom.: 2010 Cov.: 33 AF XY: 0.159 AC XY: 11807 AN XY: 74428

African (AFR) AF: 0.199 AC: 8266 AN: 41544

American (AMR) AF: 0.136 AC: 2074 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 409 AN: 3466

East Asian (EAS) AF: 0.232 AC: 1202 AN: 5176

South Asian (SAS) AF: 0.281 AC: 1355 AN: 4824

European-Finnish (FIN) AF: 0.117 AC: 1236 AN: 10590

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

European-Non Finnish (NFE) AF: 0.130 AC: 8849 AN: 68032

Other (OTH) AF: 0.148 AC: 314 AN: 2116

Alfa AF: 0.139 Hom.: 5297

Bravo AF: 0.156

Asia WGS AF: 0.244 AC: 848 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.9
DANN	Benign	0.77
PhyloP100		0.50
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: rs9332998; hg19: chr1-47404186; COSMIC: COSV60222807; COSMIC: COSV60222807;