rs7513658

Variant names:

• chr1-46811147-G-A
• rs7513658
• NM_001099772.2:c.330G>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001099772.2(CYP4B1):​c.330G>A​(p.Lys110Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0052 in 1,614,096 control chromosomes in the GnomAD database, including 417 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.029 (231 hom., cov: 32)
  • Exomes 𝑓: 0.0028 (186 hom.)
• Consequence: CYP4B1 NM_001099772.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.643
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 1-46811147-G-A is Benign according to our data. Variant chr1-46811147-G-A is described in ClinVar as Benign. ClinVar VariationId is 775549.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.643 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0971 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001099772.2. 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
	CYP4B1	NM_001099772.2	MANE Select	c.330G>A	p.Lys110Lys	synonymous	Exon 3 of 12	NP_001093242.1	P13584-2
	CYP4B1	NM_000779.4		c.330G>A	p.Lys110Lys	synonymous	Exon 3 of 12	NP_000770.2	P13584-1
	CYP4B1	NM_001319161.2		c.322+198G>A		intron	N/A	NP_001306090.1	Q8IZB0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP4B1	ENST00000371923.9	TSL:1 MANE Select	c.330G>A	p.Lys110Lys	synonymous	Exon 3 of 12	ENSP00000360991.4	P13584-2
	CYP4B1	ENST00000271153.8	TSL:1	c.330G>A	p.Lys110Lys	synonymous	Exon 3 of 12	ENSP00000271153.4	P13584-1
	CYP4B1	ENST00000371919.8	TSL:1	c.322+198G>A		intron	N/A	ENSP00000360987.4	Q8IZB0

Frequencies

GnomAD3 genomes AF: 0.0286 AC: 4352 AN: 152098 Hom.: 231 Cov.: 32

Gnomad AFR AF: 0.0998

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0103

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000397

Gnomad OTH AF: 0.0158

GnomAD2 exomes AF: 0.00708 AC: 1780 AN: 251392 AF XY: 0.00501

Gnomad AFR exome AF: 0.0986

Gnomad AMR exome AF: 0.00399

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000158

Gnomad OTH exome AF: 0.00310

GnomAD4 exome AF: 0.00277 AC: 4044 AN: 1461880 Hom.: 186 Cov.: 32 AF XY: 0.00228 AC XY: 1659 AN XY: 727240

African (AFR) AF: 0.100 AC: 3363 AN: 33472

American (AMR) AF: 0.00432 AC: 193 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

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

South Asian (SAS) AF: 0.0000927 AC: 8 AN: 86258

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

Middle Eastern (MID) AF: 0.00225 AC: 13 AN: 5768

European-Non Finnish (NFE) AF: 0.000103 AC: 114 AN: 1112006

Other (OTH) AF: 0.00584 AC: 353 AN: 60396

GnomAD4 genome AF: 0.0286 AC: 4355 AN: 152216 Hom.: 231 Cov.: 32 AF XY: 0.0278 AC XY: 2068 AN XY: 74434

African (AFR) AF: 0.0996 AC: 4135 AN: 41516

American (AMR) AF: 0.0103 AC: 157 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

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

European-Non Finnish (NFE) AF: 0.000397 AC: 27 AN: 68026

Other (OTH) AF: 0.0157 AC: 33 AN: 2108

Alfa AF: 0.0120 Hom.: 237

Bravo AF: 0.0322

Asia WGS AF: 0.00375 AC: 13 AN: 3478

EpiCase AF: 0.000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions as Germline

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	-0.41
CADD	Benign	2.9
DANN	Benign	0.64
PhyloP100		0.64
Mutation Taster		=290/10	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs7513658; hg19: chr1-47276819;