rs17499247

Variant names:

• chr10-35137827-A-G
• rs17499247
• NM_183011.2:c.-9A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_183011.2(CREM):​c.-9A>G variant causes a 5 prime UTR premature start codon gain 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_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.25
• Publications: 26 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: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CREM	NM_183011.2	MANE Select	c.-9A>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 8	NP_898829.1
	CREM	NM_183011.2	MANE Select	c.-9A>G		5_prime_UTR	Exon 2 of 8	NP_898829.1
	CREM	NM_001394595.1		c.-9A>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 8	NP_001381524.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CREM	ENST00000685392.1	MANE Select	c.-9A>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 8	ENSP00000509489.1
	CREM	ENST00000345491.7	TSL:1	c.-9A>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 8	ENSP00000265372.5
	CREM	ENST00000354759.7	TSL:1	c.-9A>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 8	ENSP00000346804.3

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

GnomAD2 exomes AF: 0.338 AC: 78452 AN: 232112 AF XY: 0.340

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 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

African (AFR) AF: 0.318 AC: 10049 AN: 31564

American (AMR) AF: 0.283 AC: 11204 AN: 39610

Ashkenazi Jewish (ASJ) AF: 0.388 AC: 9784 AN: 25204

East Asian (EAS) AF: 0.261 AC: 9887 AN: 37858

South Asian (SAS) AF: 0.342 AC: 27213 AN: 79616

European-Finnish (FIN) AF: 0.384 AC: 20045 AN: 52202

Middle Eastern (MID) AF: 0.336 AC: 1895 AN: 5644

European-Non Finnish (NFE) AF: 0.342 AC: 367500 AN: 1073268

Other (OTH) AF: 0.346 AC: 20047 AN: 57976

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

African (AFR) AF: 0.320 AC: 13278 AN: 41456

American (AMR) AF: 0.312 AC: 4766 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.399 AC: 1385 AN: 3470

East Asian (EAS) AF: 0.294 AC: 1521 AN: 5176

South Asian (SAS) AF: 0.348 AC: 1678 AN: 4822

European-Finnish (FIN) AF: 0.390 AC: 4104 AN: 10532

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.347 AC: 23585 AN: 67946

Other (OTH) AF: 0.350 AC: 740 AN: 2112

Alfa AF: 0.346 Hom.: 23524

Bravo AF: 0.330

Asia WGS AF: 0.352 AC: 1220 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	15
DANN	Benign	0.84
PhyloP100		2.3
PromoterAI		0.011	Neutral
Mutation Taster		=289/11	polymorphism (auto)

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

Other links and lift over

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