rs10827492

chr10-35140897-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_183011.2(CREM):c.44+3018C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 151,894 control chromosomes in the GnomAD database, including 8,753 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.34 (8753 hom., cov: 32)
• Consequence: CREM NM_183011.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.566

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CREM	NM_183011.2	c.44+3018C>T		intron_variant		ENST00000685392.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CREM	ENST00000685392.1	c.44+3018C>T		intron_variant			NM_183011.2	A1

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51333 AN: 151776 Hom.: 8725 Cov.: 32

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.312

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.294

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.345

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

GnomAD4 genome AF: 0.339 AC: 51421 AN: 151894 Hom.: 8753 Cov.: 32 AF XY: 0.340 AC XY: 25210 AN XY: 74240

Gnomad4 AFR AF: 0.321

Gnomad4 AMR AF: 0.313

Gnomad4 ASJ AF: 0.400

Gnomad4 EAS AF: 0.294

Gnomad4 SAS AF: 0.348

Gnomad4 FIN AF: 0.390

Gnomad4 NFE AF: 0.347

Gnomad4 OTH AF: 0.351

Alfa AF: 0.341 Hom.: 4721

Bravo AF: 0.330

Asia WGS AF: 0.353 AC: 1227 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.30
Dann	Benign	0.55

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

Other links and lift over

dbSNP: rs10827492; hg19: chr10-35429825;