rs6481941

Variant names:

• chr10-35151213-G-A
• rs6481941
• NM_183011.2:c.168+2722G>A

Variant summary

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

The NM_183011.2(CREM):​c.168+2722G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 152,078 control chromosomes in the GnomAD database, including 10,601 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 0.37 (10601 hom., cov: 33)
• Consequence: CREM NM_183011.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.649
• Publications: 11 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.424 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CREM	NM_183011.2	c.168+2722G>A		intron_variant	Intron 3 of 7	ENST00000685392.1	NP_898829.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CREM	ENST00000685392.1	c.168+2722G>A		intron_variant	Intron 3 of 7		NM_183011.2	ENSP00000509489.1

Frequencies

GnomAD3 genomes AF: 0.370 AC: 56287 AN: 151960 Hom.: 10566 Cov.: 33

Gnomad AFR AF: 0.429

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.317

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.369

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

GnomAD4 genome AF: 0.371 AC: 56389 AN: 152078 Hom.: 10601 Cov.: 33 AF XY: 0.370 AC XY: 27519 AN XY: 74352

African (AFR) AF: 0.429 AC: 17808 AN: 41464

American (AMR) AF: 0.325 AC: 4968 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.400 AC: 1387 AN: 3466

East Asian (EAS) AF: 0.317 AC: 1643 AN: 5180

South Asian (SAS) AF: 0.351 AC: 1695 AN: 4832

European-Finnish (FIN) AF: 0.391 AC: 4125 AN: 10556

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.348 AC: 23640 AN: 67966

Other (OTH) AF: 0.375 AC: 792 AN: 2112

Alfa AF: 0.370 Hom.: 1962

Bravo AF: 0.368

Asia WGS AF: 0.371 AC: 1288 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.49
DANN	Benign	0.37
PhyloP100		-0.65
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: rs6481941; hg19: chr10-35440141;