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GeneBe

10-35179179-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1

The NM_183011.2(CREM):c.312G>A(p.Lys104=) 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

2

Clinical Significance

Benign criteria provided, single submitter B:1

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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.37).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=2.17 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
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 UniProt
CREMNM_183011.2 linkuse as main transcriptc.312G>A p.Lys104= synonymous_variant 5/8 ENST00000685392.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CREMENST00000685392.1 linkuse as main transcriptc.312G>A p.Lys104= synonymous_variant 5/8 NM_183011.2 A1Q03060-31

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0297
AC:
4519
AN:
152160
Hom.:
222
Cov.:
33
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.:
91
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.:
31
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0298
AC:
4536
AN:
152278
Hom.:
224
Cov.:
33
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.:
53
Bravo
AF:
0.0334
Asia WGS
AF:
0.00462
AC:
17
AN:
3478
EpiCase
AF:
0.000709
EpiControl
AF:
0.000356

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 submitterclinical testingInvitaeDec 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.

Other links and lift over

dbSNP: rs11010115; hg19: chr10-35468107; COSMIC: COSV59769023; API