NM_183011.2:c.169-12841C>T

Variant names:

• chr10-35166048-C-T
• rs10827493
• NM_183011.2:c.169-12841C>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.169-12841C>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 151,822 control chromosomes in the GnomAD database, including 8,377 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 (8377 hom., cov: 31)
• Consequence: CREM NM_183011.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.89
• Publications: 10 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=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_183011.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CREM	NM_183011.2	MANE Select	c.169-12841C>T		intron	N/A	NP_898829.1	Q03060-31
	CREM	NM_001394595.1		c.169-12841C>T		intron	N/A	NP_001381524.1	Q03060-16
	CREM	NM_181571.3		c.169-12841C>T		intron	N/A	NP_853549.1	Q03060-16

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CREM	ENST00000685392.1	MANE Select	c.169-12841C>T		intron	N/A	ENSP00000509489.1	Q03060-31
	CREM	ENST00000345491.7	TSL:1	c.169-12841C>T		intron	N/A	ENSP00000265372.5	Q03060-16
	CREM	ENST00000354759.7	TSL:1	c.169-12841C>T		intron	N/A	ENSP00000346804.3	Q03060-26

Frequencies

GnomAD3 genomes AF: 0.330 AC: 50074 AN: 151704 Hom.: 8350 Cov.: 31

Gnomad AFR AF: 0.292

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.295

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.347

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: 50161 AN: 151822 Hom.: 8377 Cov.: 31 AF XY: 0.332 AC XY: 24604 AN XY: 74172

African (AFR) AF: 0.293 AC: 12128 AN: 41428

American (AMR) AF: 0.309 AC: 4714 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.400 AC: 1384 AN: 3464

East Asian (EAS) AF: 0.295 AC: 1525 AN: 5168

South Asian (SAS) AF: 0.348 AC: 1679 AN: 4820

European-Finnish (FIN) AF: 0.390 AC: 4086 AN: 10468

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

European-Non Finnish (NFE) AF: 0.347 AC: 23588 AN: 67898

Other (OTH) AF: 0.347 AC: 730 AN: 2106

Alfa AF: 0.277 Hom.: 1367

Bravo AF: 0.321

Asia WGS AF: 0.350 AC: 1215 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.12
DANN	Benign	0.54
PhyloP100		-1.9
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: rs10827493; hg19: chr10-35454976;