Menu
GeneBe

10-35207028-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_183011.2(CREM):c.732A>G(p.Arg244=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00152 in 1,613,756 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0083 ( 20 hom., cov: 33)
Exomes 𝑓: 0.00081 ( 14 hom. )

Consequence

CREM
NM_183011.2 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.42
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]

Genome browser will be placed here

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=-0.44).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 10-35207028-A-G is Benign according to our data. Variant chr10-35207028-A-G is described in ClinVar as [Benign]. Clinvar id is 776508.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=2.42 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00827 (1259/152320) while in subpopulation AFR AF= 0.0274 (1140/41566). AF 95% confidence interval is 0.0261. There are 20 homozygotes in gnomad4. There are 570 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 1250 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CREMNM_183011.2 linkuse as main transcriptc.732A>G p.Arg244= synonymous_variant 7/8 ENST00000685392.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CREMENST00000685392.1 linkuse as main transcriptc.732A>G p.Arg244= synonymous_variant 7/8 NM_183011.2 A1Q03060-31

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00821
AC:
1250
AN:
152202
Hom.:
20
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0273
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00576
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000206
Gnomad OTH
AF:
0.00766
GnomAD3 exomes
AF:
0.00193
AC:
485
AN:
250996
Hom.:
7
AF XY:
0.00141
AC XY:
192
AN XY:
135690
show subpopulations
Gnomad AFR exome
AF:
0.0262
Gnomad AMR exome
AF:
0.00137
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000654
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000528
Gnomad OTH exome
AF:
0.000818
GnomAD4 exome
AF:
0.000815
AC:
1191
AN:
1461436
Hom.:
14
Cov.:
30
AF XY:
0.000730
AC XY:
531
AN XY:
727018
show subpopulations
Gnomad4 AFR exome
AF:
0.0281
Gnomad4 AMR exome
AF:
0.00148
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000104
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000414
Gnomad4 OTH exome
AF:
0.00202
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00827
AC:
1259
AN:
152320
Hom.:
20
Cov.:
33
AF XY:
0.00765
AC XY:
570
AN XY:
74480
show subpopulations
Gnomad4 AFR
AF:
0.0274
Gnomad4 AMR
AF:
0.00575
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000206
Gnomad4 OTH
AF:
0.00758
Alfa
AF:
0.00480
Hom.:
5
Bravo
AF:
0.00976
Asia WGS
AF:
0.00202
AC:
7
AN:
3478
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

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 testingInvitaeJun 29, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.44
Cadd
Benign
7.8
Dann
Benign
0.68

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: rs114020170; hg19: chr10-35495956; API