chr1-47105719-G-A

Position:

• chr1-47105719-G-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP4Z1	NM_178134.3	c.1068-409G>A		intron_variant		ENST00000334194.4	NP_835235.1
CYP4Z1	XM_024453856.2	c.954-409G>A		intron_variant			XP_024309624.1
CYP4A22-AS1	NR_189276.1	n.1115-7299C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP4Z1	ENST00000334194.4	c.1068-409G>A		intron_variant		1	NM_178134.3	ENSP00000334246.3
CYP4A22-AS1	ENST00000444042.2	n.397-8542C>T		intron_variant		5

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

Gnomad4 AFR AF: 0.503

Gnomad4 AMR AF: 0.430

Gnomad4 ASJ AF: 0.271

Gnomad4 EAS AF: 0.961

Gnomad4 SAS AF: 0.656

Gnomad4 FIN AF: 0.409

Gnomad4 NFE AF: 0.342

Gnomad4 OTH AF: 0.416

Alfa AF: 0.357 Hom.: 16535

Bravo AF: 0.431

Asia WGS AF: 0.772 AC: 2682 AN: 3478

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Pulmonary disease, chronic obstructive, susceptibility to Other:1

association, no assertion criteria provided

research

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

Jul 05, 2022

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.7
DANN	Benign	0.52

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

Publications

LitVar

Other links and lift over

dbSNP: rs6690005; hg19: chr1-47571391; COSMIC: COSV61964294;