rs1057108

Positions:

• chr10-35196021-T-G

Variant summary

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

The NM_183011.2(CREM):​c.598+7633T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 1,607,806 control chromosomes in the GnomAD database, including 96,394 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 (8660 hom., cov: 32)
  • Exomes 𝑓: 0.35 (87734 hom.)
• Consequence: CREM NM_183011.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.677

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=-0.89).
• 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.598+7633T>G		intron_variant		ENST00000685392.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CREM	ENST00000685392.1	c.598+7633T>G		intron_variant			NM_183011.2	A1

Frequencies

GnomAD3 genomes AF: 0.336 AC: 51028 AN: 151874 Hom.: 8631 Cov.: 32

Gnomad AFR AF: 0.312

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.310

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.294

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.389

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.344

GnomAD3 exomes AF: 0.338 AC: 84662 AN: 250244 Hom.: 14588 AF XY: 0.341 AC XY: 46070 AN XY: 135190

Gnomad AFR exome AF: 0.312

Gnomad AMR exome AF: 0.275

Gnomad ASJ exome AF: 0.397

Gnomad EAS exome AF: 0.287

Gnomad SAS exome AF: 0.347

Gnomad FIN exome AF: 0.392

Gnomad NFE exome AF: 0.351

Gnomad OTH exome AF: 0.347

GnomAD4 exome AF: 0.346 AC: 503357 AN: 1455814 Hom.: 87734 Cov.: 29 AF XY: 0.347 AC XY: 251203 AN XY: 724588

Gnomad4 AFR exome AF: 0.318

Gnomad4 AMR exome AF: 0.283

Gnomad4 ASJ exome AF: 0.391

Gnomad4 EAS exome AF: 0.266

Gnomad4 SAS exome AF: 0.347

Gnomad4 FIN exome AF: 0.385

Gnomad4 NFE exome AF: 0.349

Gnomad4 OTH exome AF: 0.350

GnomAD4 genome AF: 0.336 AC: 51120 AN: 151992 Hom.: 8660 Cov.: 32 AF XY: 0.337 AC XY: 25042 AN XY: 74294

Gnomad4 AFR AF: 0.313

Gnomad4 AMR AF: 0.310

Gnomad4 ASJ AF: 0.399

Gnomad4 EAS AF: 0.294

Gnomad4 SAS AF: 0.350

Gnomad4 FIN AF: 0.389

Gnomad4 NFE AF: 0.348

Gnomad4 OTH AF: 0.351

Alfa AF: 0.348 Hom.: 9942

Bravo AF: 0.328

Asia WGS AF: 0.356 AC: 1236 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	15
DANN	Benign	0.70

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: rs1057108; hg19: chr10-35484949; COSMIC: COSV59769464; COSMIC: COSV59769464;