10-35206928-GA-AG

Variant names:

• chr10-35206928-GA-AG
• NM_183011.2:c.632_633delGAinsAG
• CREM p.Arg211Gln

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_183011.2(CREM):​c.632_633delGAinsAG​(p.Arg211Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CREM NM_183011.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.61
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_183011.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CREM	NM_183011.2	MANE Select	c.632_633delGAinsAG	p.Arg211Gln	missense	N/A	NP_898829.1	Q03060-31
	CREM	NM_001394595.1		c.632_633delGAinsAG	p.Arg211Gln	missense	N/A	NP_001381524.1	Q03060-16
	CREM	NM_181571.3		c.632_633delGAinsAG	p.Arg211Gln	missense	N/A	NP_853549.1	Q03060-16

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CREM	ENST00000685392.1	MANE Select	c.632_633delGAinsAG	p.Arg211Gln	missense	N/A	ENSP00000509489.1	Q03060-31
	CREM	ENST00000345491.7	TSL:1	c.632_633delGAinsAG	p.Arg211Gln	missense	N/A	ENSP00000265372.5	Q03060-16
	CREM	ENST00000354759.7	TSL:1	c.479_480delGAinsAG	p.Arg160Gln	missense	N/A	ENSP00000346804.3	Q03060-26

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.6

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr10-35495856;