Variant 10-35179179-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_183011.2(CREM):c.312G>A(p.Lys104Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.006 in 1,613,922 control chromosomes in the GnomAD database, including 442 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.030 ( 224 hom., cov: 33)

Exomes 𝑓: 0.0035 ( 218 hom. )

Consequence

CREM
NM_183011.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.17

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

BP6

Variant 10-35179179-G-A is Benign according to our data. Variant chr10-35179179-G-A is described in ClinVar as [Benign]. Clinvar id is 776507.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.17 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CREM	NM_183011.2 linkuse as main transcript	c.312G>A	p.Lys104Lys	synonymous_variant	5/8	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.312G>A	p.Lys104Lys	synonymous_variant	5/8		NM_183011.2	ENSP00000509489.1		Q03060-31

Frequencies

GnomAD3 genomes

AF:

0.0297

AC:

4519

AN:

152160

Hom.:

222

Cov.:

show subpopulations

Gnomad AFR

AF:

0.104

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00864

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000779

Gnomad OTH

AF:

0.0158

GnomAD3 exomes

AF:

0.00785

AC:

1972

AN:

251136

Hom.:

AF XY:

0.00559

AC XY:

759

AN XY:

135740

show subpopulations

Gnomad AFR exome

AF:

0.107

Gnomad AMR exome

AF:

0.00437

Gnomad ASJ exome

AF:

0.000398

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000458

Gnomad OTH exome

AF:

0.00424

GnomAD4 exome

AF:

0.00352

AC:

5149

AN:

1461644

Hom.:

218

Cov.:

AF XY:

0.00305

AC XY:

2217

AN XY:

727110

show subpopulations

Gnomad4 AFR exome

AF:

0.113

Gnomad4 AMR exome

AF:

0.00503

Gnomad4 ASJ exome

AF:

0.000537

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000313

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000566

Gnomad4 OTH exome

AF:

0.00699

GnomAD4 genome

AF:

0.0298

AC:

4536

AN:

152278

Hom.:

224

Cov.:

AF XY:

0.0290

AC XY:

2160

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.104

Gnomad4 AMR

AF:

0.00863

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000779

Gnomad4 OTH

AF:

0.0156

Alfa

AF:

0.0152

Hom.:

Bravo

AF:

0.0334

Asia WGS

AF:

0.00462

AC:

AN:

3478

EpiCase

AF:

0.000709

EpiControl

AF:

0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

8.9

DANN

Benign

0.65

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