rs16935888

chr10-35143477-T-C

Variant summary

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

The NM_183011.2(CREM):c.45-4891T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 152,100 control chromosomes in the GnomAD database, including 1,944 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 0.15 (1944 hom., cov: 31)
• Consequence: CREM NM_183011.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.59

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CREM	NM_183011.2	c.45-4891T>C		intron_variant		ENST00000685392.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CREM	ENST00000685392.1	c.45-4891T>C		intron_variant			NM_183011.2	A1

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22882 AN: 151982 Hom.: 1935 Cov.: 31

Gnomad AFR AF: 0.0771

Gnomad AMI AF: 0.0824

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.236

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.164

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

GnomAD4 genome AF: 0.151 AC: 22908 AN: 152100 Hom.: 1944 Cov.: 31 AF XY: 0.152 AC XY: 11331 AN XY: 74336

Gnomad4 AFR AF: 0.0771

Gnomad4 AMR AF: 0.177

Gnomad4 ASJ AF: 0.153

Gnomad4 EAS AF: 0.236

Gnomad4 SAS AF: 0.148

Gnomad4 FIN AF: 0.210

Gnomad4 NFE AF: 0.174

Gnomad4 OTH AF: 0.172

Alfa AF: 0.169 Hom.: 2974

Bravo AF: 0.145

Asia WGS AF: 0.227 AC: 788 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	12
Dann	Benign	0.78

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: rs16935888; hg19: chr10-35432405;