19-15681317-C-T

Variant names:

• chr19-15681317-C-T
• rs672645
• NM_023944.4:c.525+798C>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.525+798C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0246 in 151,968 control chromosomes in the GnomAD database, including 16 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 0.025 (16 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CYP4F12 NM_023944.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0960
• Publications: 1 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0835 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_023944.4. 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
	CYP4F12	NM_023944.4	MANE Select	c.525+798C>T		intron	N/A	NP_076433.3	Q9HCS2-1
	CYP4F12	NR_117085.2		n.593+798C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP4F12	ENST00000550308.6	TSL:1 MANE Select	c.525+798C>T		intron	N/A	ENSP00000448998.1	Q9HCS2-1
	CYP4F12	ENST00000324632.10	TSL:1	c.525+798C>T		intron	N/A	ENSP00000321821.9	Q9HCS2-1
	CYP4F12	ENST00000517734.5	TSL:2	n.*140+798C>T		intron	N/A	ENSP00000430849.1	Q9HCS2-2

Frequencies

GnomAD3 genomes AF: 0.0244 AC: 3705 AN: 151850 Hom.: 14 Cov.: 32

Gnomad AFR AF: 0.0855

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00734

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.0172

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 100 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 60

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 90

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.0246 AC: 3732 AN: 151968 Hom.: 16 Cov.: 32 AF XY: 0.0242 AC XY: 1799 AN XY: 74284

African (AFR) AF: 0.0859 AC: 3549 AN: 41314

American (AMR) AF: 0.00726 AC: 111 AN: 15286

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

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5180

South Asian (SAS) AF: 0.000623 AC: 3 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10580

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000412 AC: 28 AN: 68004

Other (OTH) AF: 0.0170 AC: 36 AN: 2112

Alfa AF: 0.00817 Hom.: 6

Asia WGS AF: 0.00751 AC: 26 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	8.0
DANN	Benign	0.43
PhyloP100		0.096
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: rs672645; hg19: chr19-15792127;