rs2687080

Positions:

• chr7-99703526-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001256497.3(CYP3A7-CYP3A51P):​c.1497+1989C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.964 in 152,266 control chromosomes in the GnomAD database, including 70,911 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 0.96 (70911 hom., cov: 30)
• Consequence: CYP3A7-CYP3A51P NM_001256497.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0550

Genes affected

CYP3A7-CYP3A51P (HGNC:51504): (CYP3A7-CYP3A51P readthrough) This locus represents readthrough transcription between the neighboring CYP3A7 (cytochrome P450, family 3, subfamily A, polypeptide 7) and CYP3A51P (cytochrome P450, family 3, subfamily A, polypeptide 51, pseudogene) genes, which are members of the CYP3A gene cluster on chromosome 7. The downstream pseudogene is not known to be independently transcribed. The readthrough transcript includes CYP3A7 exons 1-13 and exons 2 and 13 of the pseudogene. It encodes a CYP3A isoform with a novel C-terminus. This isoform is only expressed in alleles containing a T nucleotide at the -6 position of a splice acceptor in the pseudogene, which enables correct splicing of the upstream CYP3A7 exons to the pseudogene exons. It should be noted that the reference genome sequence represents the CYP3A7_39256 T->A allele, and thus this haplotype is unlikely to produce the readthrough transcript. [provided by RefSeq, Jan 2015]

ZSCAN25 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.08).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP3A7-CYP3A51P	NM_001256497.3	c.1497+1989C>T		intron_variant			NP_001243426.2
ZSCAN25	XR_007059988.1	n.1108-19949G>A		intron_variant
ZSCAN25	XR_007059989.1	n.1050-19949G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP3A7-CYP3A51P	ENST00000620220.6	c.1416+4286C>T		intron_variant		1		ENSP00000479282.3
CYP3A7-CYP3A51P	ENST00000611620.4	c.1497+1989C>T		intron_variant		5		ENSP00000480571.1

Frequencies

GnomAD3 genomes AF: 0.964 AC: 146647 AN: 152148 Hom.: 70877 Cov.: 30

Gnomad AFR AF: 0.879

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.977

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.965

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.968

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

GnomAD4 genome AF: 0.964 AC: 146733 AN: 152266 Hom.: 70911 Cov.: 30 AF XY: 0.965 AC XY: 71825 AN XY: 74440

Gnomad4 AFR AF: 0.879

Gnomad4 AMR AF: 0.977

Gnomad4 ASJ AF: 1.00

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 1.00

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 0.999

Gnomad4 OTH AF: 0.969

Alfa AF: 0.979 Hom.: 9076

Bravo AF: 0.959

Asia WGS AF: 0.989 AC: 3439 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.31
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: rs2687080; hg19: chr7-99301149;