Variant 10-35206973-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_183011.2(CREM):c.677C>T(p.Ser226Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00343 in 1,614,030 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0024 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0035 ( 15 hom. )

Consequence

CREM
NM_183011.2 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 5.74

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:

CREM (HGNC:):

CREM links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0105317235).

BP6

Variant 10-35206973-C-T is Benign according to our data. Variant chr10-35206973-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 721155.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 360 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CREM	NM_183011.2 linkuse as main transcript	c.677C>T	p.Ser226Leu	missense_variant	7/8	ENST00000685392.1	NP_898829.1	Q03060-31

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CREM	ENST00000685392.1 linkuse as main transcript	c.677C>T	p.Ser226Leu	missense_variant	7/8		NM_183011.2	ENSP00000509489.1		Q03060-31

Frequencies

GnomAD3 genomes

AF:

0.00237

AC:

360

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000893

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00144

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00428

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00243

AC:

610

AN:

251460

Hom.:

AF XY:

0.00263

AC XY:

358

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.000738

Gnomad AMR exome

AF:

0.000492

Gnomad ASJ exome

AF:

0.000198

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000457

Gnomad FIN exome

AF:

0.000693

Gnomad NFE exome

AF:

0.00468

Gnomad OTH exome

AF:

0.00293

GnomAD4 exome

AF:

0.00354

AC:

5175

AN:

1461698

Hom.:

Cov.:

AF XY:

0.00345

AC XY:

2511

AN XY:

727156

show subpopulations

Gnomad4 AFR exome

AF:

0.000478

Gnomad4 AMR exome

AF:

0.000738

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000638

Gnomad4 FIN exome

AF:

0.00131

Gnomad4 NFE exome

AF:

0.00436

Gnomad4 OTH exome

AF:

0.00240

GnomAD4 genome

AF:

0.00236

AC:

360

AN:

152332

Hom.:

Cov.:

AF XY:

0.00231

AC XY:

172

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.000890

Gnomad4 AMR

AF:

0.00144

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.00428

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00346

Hom.:

Bravo

AF:

0.00236

TwinsUK

AF:

0.00405

AC:

ALSPAC

AF:

0.00259

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00430

AC:

ExAC

AF:

0.00279

AC:

339

EpiCase

AF:

0.00458

EpiControl

AF:

0.00468

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

0.00050

BayesDel_noAF

Pathogenic

0.23

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.34

.;T;.;.;.;.;.;T;.;.;.;.;.;.;T;.;.;.;.;.;.;.;.;.;.;.;.;.;.

Eigen

Uncertain

0.65

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Pathogenic

0.99

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

M_CAP

Uncertain

0.091

MetaRNN

Benign

0.011

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

MetaSVM

Uncertain

-0.27

PrimateAI

Uncertain

0.68

PROVEAN

Uncertain

-3.8

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

REVEL

Benign

0.29

Sift

Uncertain

0.0010

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

Sift4G

Uncertain

0.0020

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

Polyphen

1.0, 1.0, 0.99

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

Vest4

0.81

MVP

0.59

MPC

0.48

ClinPred

0.043

GERP RS

5.8

Varity_R

0.44

gMVP

0.66

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