rs1148247

chr10-35208018-G-Achr10-35208018-G-C

Variant summary

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

The NM_183011.2(CREM):c.755+967G>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 152,086 control chromosomes in the GnomAD database, including 10,078 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 (10078 hom., cov: 33)
• Consequence: CREM NM_183011.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0430

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.43 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CREM	NM_183011.2	c.755+967G>A		intron_variant		ENST00000685392.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CREM	ENST00000685392.1	c.755+967G>A		intron_variant			NM_183011.2	A1

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50274 AN: 151968 Hom.: 10085 Cov.: 33

Gnomad AFR AF: 0.0835

Gnomad AMI AF: 0.572

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.430

Gnomad EAS AF: 0.290

Gnomad SAS AF: 0.425

Gnomad FIN AF: 0.437

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.434

Gnomad OTH AF: 0.363

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

GnomAD4 genome AF: 0.330 AC: 50250 AN: 152086 Hom.: 10078 Cov.: 33 AF XY: 0.335 AC XY: 24902 AN XY: 74350

Gnomad4 AFR AF: 0.0833

Gnomad4 AMR AF: 0.407

Gnomad4 ASJ AF: 0.430

Gnomad4 EAS AF: 0.291

Gnomad4 SAS AF: 0.425

Gnomad4 FIN AF: 0.437

Gnomad4 NFE AF: 0.434

Gnomad4 OTH AF: 0.357

Alfa AF: 0.419 Hom.: 18794

Bravo AF: 0.315

Asia WGS AF: 0.291 AC: 1016 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	2.1
Dann	Benign	0.57

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: rs1148247; hg19: chr10-35496946;