rs4934736

chr10-35207940-G-A

Variant summary

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

The NM_183011.2(CREM):c.755+889G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 152,010 control chromosomes in the GnomAD database, including 8,392 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 (8392 hom., cov: 32)
• Consequence: CREM NM_183011.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.389

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) 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.755+889G>A		intron_variant		ENST00000685392.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CREM	ENST00000685392.1	c.755+889G>A		intron_variant			NM_183011.2	A1

Frequencies

GnomAD3 genomes AF: 0.330 AC: 50106 AN: 151892 Hom.: 8364 Cov.: 32

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.293

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.389

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.341

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

GnomAD4 genome AF: 0.330 AC: 50194 AN: 152010 Hom.: 8392 Cov.: 32 AF XY: 0.332 AC XY: 24623 AN XY: 74274

Gnomad4 AFR AF: 0.292

Gnomad4 AMR AF: 0.308

Gnomad4 ASJ AF: 0.400

Gnomad4 EAS AF: 0.293

Gnomad4 SAS AF: 0.348

Gnomad4 FIN AF: 0.389

Gnomad4 NFE AF: 0.348

Gnomad4 OTH AF: 0.348

Alfa AF: 0.333 Hom.: 1065

Bravo AF: 0.321

Asia WGS AF: 0.352 AC: 1224 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.29
Dann	Benign	0.38

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: rs4934736; hg19: chr10-35496868;