rs11085971

Variant names:

• chr19-15686003-G-T
• rs11085971
• NM_023944.4:c.1115+806G>T

Variant summary

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

The NM_023944.4(CYP4F12):​c.1115+806G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0488 in 152,116 control chromosomes in the GnomAD database, including 281 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 0.049 (281 hom., cov: 32)
• Consequence: CYP4F12 NM_023944.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.244
• Publications: 8 publications found

Genes affected

CYP4F12 (HGNC:18857): (cytochrome P450 family 4 subfamily F member 12) 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 likely localizes to the endoplasmic reticulum. When expressed in yeast the enzyme is capable of oxdizing arachidonic acid. It can also catalyze the epoxidation of 22:6n-3 and 22:5n-3 polyunsaturated long-chain fatty acids. This gene is part of a cluster of cytochrome P450 genes on chromosome 19. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2014]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0758 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP4F12	NM_023944.4	c.1115+806G>T		intron_variant	Intron 9 of 12	ENST00000550308.6	NP_076433.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP4F12	ENST00000550308.6	c.1115+806G>T		intron_variant	Intron 9 of 12	1	NM_023944.4	ENSP00000448998.1
CYP4F12	ENST00000517734.5	n.*1782+806G>T		intron_variant	Intron 8 of 10	2		ENSP00000430849.1

Frequencies

GnomAD3 genomes AF: 0.0489 AC: 7432 AN: 152000 Hom.: 282 Cov.: 32

Gnomad AFR AF: 0.0150

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.0271

Gnomad ASJ AF: 0.0118

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0180

Gnomad FIN AF: 0.0806

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0776

Gnomad OTH AF: 0.0387

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

GnomAD4 genome AF: 0.0488 AC: 7426 AN: 152116 Hom.: 281 Cov.: 32 AF XY: 0.0469 AC XY: 3488 AN XY: 74334

African (AFR) AF: 0.0150 AC: 621 AN: 41504

American (AMR) AF: 0.0270 AC: 413 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0118 AC: 41 AN: 3470

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5172

South Asian (SAS) AF: 0.0178 AC: 86 AN: 4824

European-Finnish (FIN) AF: 0.0806 AC: 849 AN: 10540

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

European-Non Finnish (NFE) AF: 0.0775 AC: 5273 AN: 68004

Other (OTH) AF: 0.0383 AC: 81 AN: 2116

Alfa AF: 0.0628 Hom.: 197

Bravo AF: 0.0444

Asia WGS AF: 0.0100 AC: 35 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	12
DANN	Benign	0.90
PhyloP100		0.24
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: rs11085971; hg19: chr19-15796813;