chr1-46813516-C-T

Variant names:

• chr1-46813516-C-T
• rs1243643974
• NM_001099772.2:c.530C>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001099772.2(CYP4B1):​c.530C>T​(p.Ser177Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S177Y) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CYP4B1 NM_001099772.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.35

Genes affected

CYP4B1 (HGNC:2644): (cytochrome P450 family 4 subfamily B member 1) 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. In rodents, the homologous protein has been shown to metabolize certain carcinogens; however, the specific function of the human protein has not been determined. Multiple transcript variants have been found for this gene. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.42145336).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP4B1	NM_001099772.2	c.530C>T	p.Ser177Phe	missense_variant	Exon 5 of 12	ENST00000371923.9	NP_001093242.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP4B1	ENST00000371923.9	c.530C>T	p.Ser177Phe	missense_variant	Exon 5 of 12	1	NM_001099772.2	ENSP00000360991.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251192 Hom.: 0 AF XY: 0.00000737 AC XY: 1 AN XY: 135740

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Benign	-0.026	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.072	T;.;T;.;T;.
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.80	T;T;T;T;.;T
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.42	T;T;T;T;T;T
MetaSVM	Uncertain	0.29	D
MutationAssessor	Uncertain	2.8	.;M;M;.;.;.
PrimateAI	Benign	0.40	T
PROVEAN	Pathogenic	-4.7	.;D;D;D;.;D
REVEL	Uncertain	0.36
Sift	Benign	0.044	.;D;D;D;.;D
Sift4G	Uncertain	0.038	.;D;D;T;D;D
Polyphen		0.51, 0.56, 0.99	.;P;P;D;.;.
Vest4		0.40, 0.43, 0.44, 0.43
MutPred		0.49		Loss of disorder (P = 0.0182);Loss of disorder (P = 0.0182);Loss of disorder (P = 0.0182);.;Loss of disorder (P = 0.0182);.;
MVP		0.75
MPC		0.45
ClinPred		0.89	D
GERP RS		0.81
Varity_R		0.65
gMVP		0.16

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1243643974; hg19: chr1-47279188;