Variant 6-136179077-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_018945.4(PDE7B):c.884A>G(p.Lys295Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00147 in 1,614,108 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0063 ( 10 hom., cov: 32)

Exomes 𝑓: 0.00097 ( 11 hom. )

Consequence

PDE7B
NM_018945.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.06

Variant links:

Genes affected

PDE7B (HGNC:8792): (phosphodiesterase 7B) The 3',5'-cyclic nucleotides cAMP and cGMP function as second messengers in a wide variety of signal transduction pathways. 3',5'-cyclic nucleotide phosphodiesterases (PDEs) catalyze the hydrolysis of cAMP and cGMP to the corresponding 5'-monophosphates and provide a mechanism to downregulate cAMP and cGMP signaling. This gene encodes a cAMP-specific phosphodiesterase, a member of the cyclic nucleotide phosphodiesterase family.[provided by RefSeq, Apr 2009]

PDE7B links:

PDE7B-AS1 (HGNC:56334): (PDE7B antisense RNA 1)

PDE7B-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004003942).

BP6

Variant 6-136179077-A-G is Benign according to our data. Variant chr6-136179077-A-G is described in ClinVar as [Benign]. Clinvar id is 775242.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00628 (956/152338) while in subpopulation AFR AF= 0.0215 (893/41564). AF 95% confidence interval is 0.0203. There are 10 homozygotes in gnomad4. There are 462 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 956 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE7B	NM_018945.4 linkuse as main transcript	c.884A>G	p.Lys295Arg	missense_variant	10/13	ENST00000308191.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE7B	ENST00000308191.11 linkuse as main transcript	c.884A>G	p.Lys295Arg	missense_variant	10/13	1	NM_018945.4	P1
PDE7B-AS1	ENST00000655618.1 linkuse as main transcript	n.82-16729T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.00627

AC:

955

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0215

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00242

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00525

GnomAD3 exomes

AF:

0.00165

AC:

415

AN:

251414

Hom.:

AF XY:

0.00132

AC XY:

179

AN XY:

135878

show subpopulations

Gnomad AFR exome

AF:

0.0207

Gnomad AMR exome

AF:

0.00107

Gnomad ASJ exome

AF:

0.000496

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000246

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.000965

AC:

1411

AN:

1461770

Hom.:

Cov.:

AF XY:

0.000921

AC XY:

670

AN XY:

727210

show subpopulations

Gnomad4 AFR exome

AF:

0.0220

Gnomad4 AMR exome

AF:

0.00103

Gnomad4 ASJ exome

AF:

0.000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000418

Gnomad4 OTH exome

AF:

0.00199

GnomAD4 genome

AF:

0.00628

AC:

956

AN:

152338

Hom.:

Cov.:

AF XY:

0.00620

AC XY:

462

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.0215

Gnomad4 AMR

AF:

0.00242

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00141

Hom.:

Bravo

AF:

0.00717

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0177

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00204

AC:

248

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000533

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 27, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.83

DEOGEN2

Benign

0.26

T;T

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.12

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.80

T;T

MetaRNN

Benign

0.0040

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-0.41

N;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.36

PROVEAN

Benign

0.21

N;.

REVEL

Benign

0.24

Sift

Benign

0.75

T;.

Sift4G

Benign

0.66

T;T

Polyphen

0.0

B;B

Vest4

0.15

MVP

0.16

MPC

0.26

ClinPred

0.0083

GERP RS

3.3

Varity_R

0.092

gMVP

0.36

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over