rs150968551

Variant names:

• chr1-46962886-T-G
• rs150968551
• NM_001320289.2:c.174+1130T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001320289.2(CYP4X1):​c.174+1130T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0167 in 152,310 control chromosomes in the GnomAD database, including 36 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 0.017 (36 hom., cov: 32)
• Consequence: CYP4X1 NM_001320289.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0770
• Publications: 1 publications found

Genes affected

CYP4X1 (HGNC:20244): (cytochrome P450 family 4 subfamily X member 1) This gene encodes a member of the cytochrome P450 superfamily of enzymes and is located within a cluster of genes belonging to this superfamily on chromosome 1. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. The expression pattern of a similar rat protein suggests that this protein may be involved in neurovascular function in the brain. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0167 (2540/152310) while in subpopulation SAS AF = 0.0459 (221/4820). AF 95% confidence interval is 0.0409. There are 36 homozygotes in GnomAd4. There are 1224 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 36 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP4X1	NM_001320289.2	c.174+1130T>G		intron_variant	Intron 1 of 11		NP_001307218.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.0167 AC: 2536 AN: 152192 Hom.: 36 Cov.: 32

Gnomad AFR AF: 0.0303

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0113

Gnomad ASJ AF: 0.0173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0456

Gnomad FIN AF: 0.00734

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0104

Gnomad OTH AF: 0.0163

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

GnomAD4 genome AF: 0.0167 AC: 2540 AN: 152310 Hom.: 36 Cov.: 32 AF XY: 0.0164 AC XY: 1224 AN XY: 74480

African (AFR) AF: 0.0303 AC: 1260 AN: 41552

American (AMR) AF: 0.0113 AC: 173 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0173 AC: 60 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.0459 AC: 221 AN: 4820

European-Finnish (FIN) AF: 0.00734 AC: 78 AN: 10628

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0104 AC: 708 AN: 68030

Other (OTH) AF: 0.0161 AC: 34 AN: 2112

Alfa AF: 0.0156 Hom.: 5

Bravo AF: 0.0168

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	2.8
DANN	Benign	0.94
PhyloP100		0.077
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs150968551; hg19: chr1-47428558; COSMIC: COSV73331888;