Variant 10-35211745-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000345491.7(CREM):c.845A>G(p.Lys282Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000818 in 1,614,044 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0044 ( 6 hom., cov: 32)

Exomes 𝑓: 0.00044 ( 3 hom. )

Consequence

CREM
ENST00000345491.7 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.59

Variant links:

Genes affected

CREM (HGNC:2352): (cAMP responsive element modulator) This gene encodes a bZIP transcription factor that binds to the cAMP responsive element found in many viral and cellular promoters. It is an important component of cAMP-mediated signal transduction during the spermatogenetic cycle, as well as other complex processes. Alternative promoter and translation initiation site usage allows this gene to exert spatial and temporal specificity to cAMP responsiveness. Multiple alternatively spliced transcript variants encoding several different isoforms have been found for this gene, with some of them functioning as activators and some as repressors of transcription. [provided by RefSeq, Jul 2008]

CREM links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009129018).

BP6

Variant 10-35211745-A-G is Benign according to our data. Variant chr10-35211745-A-G is described in ClinVar as [Benign]. Clinvar id is 712044.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd at 667 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CREM	NM_183011.2 linkuse as main transcript	c.*347A>G		3_prime_UTR_variant	8/8	ENST00000685392.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CREM	ENST00000685392.1 linkuse as main transcript	c.*347A>G		3_prime_UTR_variant	8/8		NM_183011.2	A1	Q03060-31

Frequencies

GnomAD3 genomes

AF:

0.00438

AC:

667

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0149

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00268

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00119

AC:

300

AN:

251186

Hom.:

AF XY:

0.000877

AC XY:

119

AN XY:

135754

show subpopulations

Gnomad AFR exome

AF:

0.0163

Gnomad AMR exome

AF:

0.000725

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000164

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000443

AC:

647

AN:

1461712

Hom.:

Cov.:

AF XY:

0.000404

AC XY:

294

AN XY:

727140

show subpopulations

Gnomad4 AFR exome

AF:

0.0156

Gnomad4 AMR exome

AF:

0.000806

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000928

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000719

Gnomad4 OTH exome

AF:

0.00118

GnomAD4 genome

AF:

0.00442

AC:

673

AN:

152332

Hom.:

Cov.:

AF XY:

0.00430

AC XY:

320

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.0150

Gnomad4 AMR

AF:

0.00268

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.000713

Hom.:

Bravo

AF:

0.00487

ESP6500AA

AF:

0.0127

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00149

AC:

181

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

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

Invitae

Jul 06, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.35

Cadd

Benign

Dann

Uncertain

0.99

Eigen

Benign

0.16

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.94

D;D;D;D;D;.;D;D;D;D;D;D;D;D;D;D

MetaRNN

Benign

0.0091

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.95

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;D;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-0.48

N;N;N;N;N;N;N;N;N;N;N;D;N;N;N;N

REVEL

Benign

0.081

Sift

Benign

0.030

D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D

Sift4G

Uncertain

0.029

D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D

Polyphen

0.57, 0.61, 0.21, 0.22

.;.;.;P;.;.;P;.;.;.;P;.;B;B;.;.

Vest4

0.29

MVP

0.29

MPC

0.17

ClinPred

0.024

GERP RS

6.0

Varity_R

0.15

gMVP

0.33

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