NM_000761.5:c.*1187G>A

Variant names:

• chr15-74756275-G-A
• rs45599945
• NM_000761.5:c.*1187G>A

Variant summary

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

The NM_000761.5(CYP1A2):​c.*1187G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0074 in 151,864 control chromosomes in the GnomAD database, including 19 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 0.0074 (19 hom., cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CYP1A2 NM_000761.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.252
• Publications: 2 publications found

Genes affected

CYP1A2 (HGNC:2596): (cytochrome P450 family 1 subfamily A member 2) 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. The protein encoded by this gene localizes to the endoplasmic reticulum and its expression is induced by some polycyclic aromatic hydrocarbons (PAHs), some of which are found in cigarette smoke. The enzyme's endogenous substrate is unknown; however, it is able to metabolize some PAHs to carcinogenic intermediates. Other xenobiotic substrates for this enzyme include caffeine, aflatoxin B1, and acetaminophen. The transcript from this gene contains four Alu sequences flanked by direct repeats in the 3' untranslated region. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0074 (1124/151864) while in subpopulation AFR AF = 0.0261 (1080/41410). AF 95% confidence interval is 0.0248. There are 19 homozygotes in GnomAd4. There are 509 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1124 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000761.5. 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
	CYP1A2	NM_000761.5	MANE Select	c.*1187G>A		3_prime_UTR	Exon 7 of 7	NP_000752.2	P05177

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP1A2	ENST00000343932.5	TSL:1 MANE Select	c.*1187G>A		3_prime_UTR	Exon 7 of 7	ENSP00000342007.4	P05177
	CYP1A2	ENST00000872476.1		c.*1187G>A		3_prime_UTR	Exon 7 of 7	ENSP00000542535.1
	CYP1A2	ENST00000872478.1		c.*1187G>A		3_prime_UTR	Exon 7 of 7	ENSP00000542537.1

Frequencies

GnomAD3 genomes AF: 0.00741 AC: 1124 AN: 151746 Hom.: 19 Cov.: 31

Gnomad AFR AF: 0.0262

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00204

Gnomad ASJ AF: 0.000289

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00431

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 36 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 28

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 26

Other (OTH) AF: 0.00 AC: 0 AN: 6

GnomAD4 genome AF: 0.00740 AC: 1124 AN: 151864 Hom.: 19 Cov.: 31 AF XY: 0.00686 AC XY: 509 AN XY: 74212

African (AFR) AF: 0.0261 AC: 1080 AN: 41410

American (AMR) AF: 0.00204 AC: 31 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.000289 AC: 1 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5156

South Asian (SAS) AF: 0.00 AC: 0 AN: 4802

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10546

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67952

Other (OTH) AF: 0.00427 AC: 9 AN: 2110

Alfa AF: 0.00693 Hom.: 0

Bravo AF: 0.00827

Asia WGS AF: 0.00231 AC: 9 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	5.7
DANN	Benign	0.41
PhyloP100		0.25

Splicing

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

Other links and lift over

dbSNP: rs45599945; hg19: chr15-75048616;