rs10808746

Positions:

• chr8-65732478-G-A

Variant summary

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

The NM_001242318.3(PDE7A):​c.696+2316C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.597 in 152,066 control chromosomes in the GnomAD database, including 29,885 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 0.60 (29885 hom., cov: 31)
• Consequence: PDE7A NM_001242318.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.340

Genes affected

PDE7A (HGNC:8791): (phosphodiesterase 7A) The protein encoded by this gene belongs to the cyclic nucleotide phosphodiesterase (PDE) family, and PDE7 subfamily. This PDE hydrolyzes the second messenger, cAMP, which is a regulator and mediator of a number of cellular responses to extracellular signals. Thus, by regulating the cellular concentration of cAMP, this protein plays a key role in many important physiological processes. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2011]

MTFR1 (HGNC:29510): (mitochondrial fission regulator 1) This gene encodes a mitochondrial protein that is characterized by a poly-proline rich region. A chicken homolog of this protein promotes mitochondrial fission and the mouse homolog protects cells from oxidative stress. A related pseudogene of this gene is found on chromosome X. [provided by RefSeq, Mar 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.885 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE7A	NM_001242318.3	c.696+2316C>T		intron_variant		ENST00000401827.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE7A	ENST00000401827.8	c.696+2316C>T		intron_variant		1	NM_001242318.3	P4

Frequencies

GnomAD3 genomes AF: 0.597 AC: 90705 AN: 151948 Hom.: 29820 Cov.: 31

Gnomad AFR AF: 0.892

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.584

Gnomad ASJ AF: 0.517

Gnomad EAS AF: 0.613

Gnomad SAS AF: 0.599

Gnomad FIN AF: 0.495

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.441

Gnomad OTH AF: 0.578

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

GnomAD4 genome AF: 0.597 AC: 90831 AN: 152066 Hom.: 29885 Cov.: 31 AF XY: 0.602 AC XY: 44751 AN XY: 74324

Gnomad4 AFR AF: 0.892

Gnomad4 AMR AF: 0.584

Gnomad4 ASJ AF: 0.517

Gnomad4 EAS AF: 0.613

Gnomad4 SAS AF: 0.598

Gnomad4 FIN AF: 0.495

Gnomad4 NFE AF: 0.441

Gnomad4 OTH AF: 0.579

Alfa AF: 0.481 Hom.: 23558

Bravo AF: 0.614

Asia WGS AF: 0.667 AC: 2316 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.52
DANN	Benign	0.35

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: rs10808746; hg19: chr8-66644713;