10-35199336-C-T

Variant names:

• chr10-35199336-C-T
• rs12775799
• NM_183011.2:c.599-7559C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_183011.2(CREM):​c.599-7559C>T 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 152,042 control chromosomes in the GnomAD database, including 8,403 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 (8403 hom., cov: 33)
• Consequence: CREM NM_183011.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.842
• Publications: 12 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 -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 rank	MANE	Protein	UniProt
CREM	NM_183011.2	c.599-7559C>T		intron_variant	Intron 6 of 7	ENST00000685392.1	NP_898829.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CREM	ENST00000685392.1	c.599-7559C>T		intron_variant	Intron 6 of 7		NM_183011.2	ENSP00000509489.1

Frequencies

GnomAD3 genomes AF: 0.330 AC: 50148 AN: 151924 Hom.: 8375 Cov.: 33

Gnomad AFR AF: 0.292

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.398

Gnomad EAS AF: 0.294

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.389

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.340

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

GnomAD4 genome AF: 0.330 AC: 50236 AN: 152042 Hom.: 8403 Cov.: 33 AF XY: 0.332 AC XY: 24642 AN XY: 74302

African (AFR) AF: 0.293 AC: 12139 AN: 41490

American (AMR) AF: 0.308 AC: 4708 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.398 AC: 1380 AN: 3464

East Asian (EAS) AF: 0.294 AC: 1525 AN: 5180

South Asian (SAS) AF: 0.348 AC: 1676 AN: 4820

European-Finnish (FIN) AF: 0.389 AC: 4092 AN: 10524

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.348 AC: 23655 AN: 67976

Other (OTH) AF: 0.347 AC: 733 AN: 2112

Alfa AF: 0.247 Hom.: 763

Bravo AF: 0.321

Asia WGS AF: 0.354 AC: 1231 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	0.076
DANN	Benign	0.57
PhyloP100		-0.84
Mutation Taster		=100/0	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: rs12775799; hg19: chr10-35488264;