rs17499247

Positions:

• chr10-35137827-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_183011.2(CREM):​c.-9A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 1,554,926 control chromosomes in the GnomAD database, including 91,306 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 (8743 hom., cov: 32)
  • Exomes 𝑓: 0.34 (82563 hom.)
• Consequence: CREM NM_183011.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.25

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CREM	NM_183011.2	c.-9A>G		5_prime_UTR_variant	2/8	ENST00000685392.1	NP_898829.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CREM	ENST00000685392.1	c.-9A>G		5_prime_UTR_variant	2/8		NM_183011.2	ENSP00000509489	A1

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51297 AN: 151864 Hom.: 8714 Cov.: 32

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.312

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.294

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.344

GnomAD3 exomes AF: 0.338 AC: 78452 AN: 232112 Hom.: 13590 AF XY: 0.340 AC XY: 42867 AN XY: 126254

Gnomad AFR exome AF: 0.320

Gnomad AMR exome AF: 0.275

Gnomad ASJ exome AF: 0.398

Gnomad EAS exome AF: 0.281

Gnomad SAS exome AF: 0.346

Gnomad FIN exome AF: 0.392

Gnomad NFE exome AF: 0.348

Gnomad OTH exome AF: 0.345

GnomAD4 exome AF: 0.340 AC: 477624 AN: 1402942 Hom.: 82563 Cov.: 25 AF XY: 0.342 AC XY: 238850 AN XY: 699024

Gnomad4 AFR exome AF: 0.318

Gnomad4 AMR exome AF: 0.283

Gnomad4 ASJ exome AF: 0.388

Gnomad4 EAS exome AF: 0.261

Gnomad4 SAS exome AF: 0.342

Gnomad4 FIN exome AF: 0.384

Gnomad4 NFE exome AF: 0.342

Gnomad4 OTH exome AF: 0.346

GnomAD4 genome AF: 0.338 AC: 51387 AN: 151984 Hom.: 8743 Cov.: 32 AF XY: 0.339 AC XY: 25179 AN XY: 74270

Gnomad4 AFR AF: 0.320

Gnomad4 AMR AF: 0.312

Gnomad4 ASJ AF: 0.399

Gnomad4 EAS AF: 0.294

Gnomad4 SAS AF: 0.348

Gnomad4 FIN AF: 0.390

Gnomad4 NFE AF: 0.347

Gnomad4 OTH AF: 0.350

Alfa AF: 0.350 Hom.: 14071

Bravo AF: 0.330

Asia WGS AF: 0.352 AC: 1220 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	15
DANN	Benign	0.84

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: rs17499247; hg19: chr10-35426755; COSMIC: COSV61319702; COSMIC: COSV61319702;