rs4934735

Positions:

• chr10-35207802-A-G
• chr10-35207802-A-T

Variant summary

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

The NM_183011.2(CREM):​c.755+751A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 151,808 control chromosomes in the GnomAD database, including 8,559 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 0.33 (8559 hom., cov: 32)
• Consequence: CREM NM_183011.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32

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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CREM	NM_183011.2	c.755+751A>G		intron_variant		ENST00000685392.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CREM	ENST00000685392.1	c.755+751A>G		intron_variant			NM_183011.2	A1

Frequencies

GnomAD3 genomes AF: 0.334 AC: 50591 AN: 151690 Hom.: 8532 Cov.: 32

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.310

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.294

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.399

Gnomad MID AF: 0.325

Gnomad NFE AF: 0.352

Gnomad OTH AF: 0.345

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

GnomAD4 genome AF: 0.334 AC: 50678 AN: 151808 Hom.: 8559 Cov.: 32 AF XY: 0.335 AC XY: 24845 AN XY: 74168

Gnomad4 AFR AF: 0.294

Gnomad4 AMR AF: 0.311

Gnomad4 ASJ AF: 0.400

Gnomad4 EAS AF: 0.294

Gnomad4 SAS AF: 0.349

Gnomad4 FIN AF: 0.399

Gnomad4 NFE AF: 0.352

Gnomad4 OTH AF: 0.352

Alfa AF: 0.282 Hom.: 1411

Bravo AF: 0.323

Asia WGS AF: 0.353 AC: 1226 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.0030
DANN	Benign	0.25

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: rs4934735; hg19: chr10-35496730;