rs6690005

Variant names:

• chr1-47105719-G-A
• rs6690005
• NM_178134.3:c.1068-409G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-47105719-G-A
• chr1-47105719-G-C

Variant summary

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

The NM_178134.3(CYP4Z1):​c.1068-409G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 151,986 control chromosomes in the GnomAD database, including 15,422 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency: Genomes: 𝑓 0.43 (15422 hom., cov: 32)
• Consequence: CYP4Z1 NM_178134.3 intron
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: 0.171
• Publications: 3 publications found

Genes affected

CYP4Z1 (HGNC:20583): (cytochrome P450 family 4 subfamily Z 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 gene is part of a cluster of cytochrome P450 genes on chromosome 1p33. [provided by RefSeq, Jul 2008]

CYP4A22-AS1 (HGNC:43715): (CYP4A22 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.939 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178134.3. 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
	CYP4Z1	NM_178134.3	MANE Select	c.1068-409G>A		intron	N/A	NP_835235.1	Q86W10
	CYP4A22-AS1	NR_189276.1		n.1115-7299C>T		intron	N/A
	CYP4A22-AS1	NR_199717.1		n.1161-7299C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP4Z1	ENST00000334194.4	TSL:1 MANE Select	c.1068-409G>A		intron	N/A	ENSP00000334246.3	Q86W10
	CYP4A22-AS1	ENST00000444042.2	TSL:5	n.397-8542C>T		intron	N/A
	CYP4A22-AS1	ENST00000815597.1		n.1124-7299C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.430 AC: 65304 AN: 151868 Hom.: 15388 Cov.: 32

Gnomad AFR AF: 0.503

Gnomad AMI AF: 0.425

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.961

Gnomad SAS AF: 0.658

Gnomad FIN AF: 0.409

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.342

Gnomad OTH AF: 0.410

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

GnomAD4 genome AF: 0.430 AC: 65393 AN: 151986 Hom.: 15422 Cov.: 32 AF XY: 0.442 AC XY: 32820 AN XY: 74300

African (AFR) AF: 0.503 AC: 20838 AN: 41428

American (AMR) AF: 0.430 AC: 6564 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.271 AC: 941 AN: 3468

East Asian (EAS) AF: 0.961 AC: 4970 AN: 5170

South Asian (SAS) AF: 0.656 AC: 3163 AN: 4820

European-Finnish (FIN) AF: 0.409 AC: 4325 AN: 10564

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.342 AC: 23239 AN: 67956

Other (OTH) AF: 0.416 AC: 878 AN: 2110

Alfa AF: 0.370 Hom.: 28987

Bravo AF: 0.431

Asia WGS AF: 0.772 AC: 2682 AN: 3478

ClinVar

ClinVar submissions

Significance: association

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	-	Pulmonary disease, chronic obstructive, susceptibility to (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.7
DANN	Benign	0.52
PhyloP100		0.17
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: rs6690005; hg19: chr1-47571391; COSMIC: COSV61964294;