chr7-99652376-G-A

Variant names:

• chr7-99652376-G-A
• rs6976017
• NM_000777.5:c.1253+177C>T

Variant summary

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

The ENST00000222982.8(CYP3A5):​c.1253+177C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0511 in 498,110 control chromosomes in the GnomAD database, including 951 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 0.068 (488 hom., cov: 32)
  • Exomes 𝑓: 0.044 (463 hom.)
• Consequence: CYP3A5 ENST00000222982.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.24
• Publications: 9 publications found

Genes affected

CYP3A5 (HGNC:2638): (cytochrome P450 family 3 subfamily A member 5) 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 encoded protein metabolizes drugs as well as the steroid hormones testosterone and progesterone. This gene is part of a cluster of cytochrome P450 genes on chromosome 7q21.1. Two pseudogenes of this gene have been identified within this cluster on chromosome 7. Expression of this gene is widely variable among populations, and a single nucleotide polymorphism that affects transcript splicing has been associated with susceptibility to hypertensions. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2014]

ZSCAN25 (HGNC:21961): (zinc finger and SCAN domain containing 25) This gene encodes a protein that bears some similarity to zinc finger proteins, which are involved in DNA binding and protein-protein interactions. Multiple alternatively spliced transcript variants have been identified, but the full-length nature for most of them has not been determined. [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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000222982.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP3A5	NM_000777.5	MANE Select	c.1253+177C>T		intron	N/A	NP_000768.1
	CYP3A5	NM_001291830.2		c.1223+177C>T		intron	N/A	NP_001278759.1
	CYP3A5	NM_001291829.2		c.914+177C>T		intron	N/A	NP_001278758.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP3A5	ENST00000222982.8	TSL:1 MANE Select	c.1253+177C>T		intron	N/A	ENSP00000222982.4
	CYP3A5	ENST00000488187.1	TSL:5	n.508C>T		non_coding_transcript_exon	Exon 2 of 2
	CYP3A5	ENST00000461920.5	TSL:2	n.1845+177C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0676 AC: 10268 AN: 151884 Hom.: 490 Cov.: 32

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.0612

Gnomad ASJ AF: 0.0389

Gnomad EAS AF: 0.0262

Gnomad SAS AF: 0.0448

Gnomad FIN AF: 0.0502

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0434

Gnomad OTH AF: 0.0558

GnomAD4 exome AF: 0.0438 AC: 15171 AN: 346106 Hom.: 463 Cov.: 4 AF XY: 0.0430 AC XY: 7699 AN XY: 179208

African (AFR) AF: 0.122 AC: 1267 AN: 10420

American (AMR) AF: 0.0663 AC: 787 AN: 11870

Ashkenazi Jewish (ASJ) AF: 0.0360 AC: 404 AN: 11228

East Asian (EAS) AF: 0.0191 AC: 506 AN: 26528

South Asian (SAS) AF: 0.0358 AC: 806 AN: 22496

European-Finnish (FIN) AF: 0.0538 AC: 1374 AN: 25542

Middle Eastern (MID) AF: 0.0207 AC: 34 AN: 1640

European-Non Finnish (NFE) AF: 0.0417 AC: 8999 AN: 215590

Other (OTH) AF: 0.0478 AC: 994 AN: 20792

GnomAD4 genome AF: 0.0676 AC: 10275 AN: 152004 Hom.: 488 Cov.: 32 AF XY: 0.0658 AC XY: 4887 AN XY: 74308

African (AFR) AF: 0.126 AC: 5197 AN: 41396

American (AMR) AF: 0.0612 AC: 934 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.0389 AC: 135 AN: 3472

East Asian (EAS) AF: 0.0263 AC: 136 AN: 5180

South Asian (SAS) AF: 0.0454 AC: 219 AN: 4820

European-Finnish (FIN) AF: 0.0502 AC: 530 AN: 10558

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0434 AC: 2951 AN: 68006

Other (OTH) AF: 0.0552 AC: 116 AN: 2102

Alfa AF: 0.0310 Hom.: 22

Bravo AF: 0.0718

Asia WGS AF: 0.0530 AC: 184 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.042
DANN	Benign	0.69
PhyloP100		-3.2
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: rs6976017; hg19: chr7-99249999;