10-35193037-G-T

Variant names:

• chr10-35193037-G-T
• rs7077242
• NM_183011.2:c.598+4649G>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.598+4649G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 151,874 control chromosomes in the GnomAD database, including 8,416 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 (8416 hom., cov: 32)
• Consequence: CREM NM_183011.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0610
• 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=-0.88).
• 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.598+4649G>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.598+4649G>T		intron_variant	Intron 6 of 7		NM_183011.2	ENSP00000509489.1

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50175 AN: 151756 Hom.: 8388 Cov.: 32

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.295

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.341

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

GnomAD4 genome AF: 0.331 AC: 50263 AN: 151874 Hom.: 8416 Cov.: 32 AF XY: 0.332 AC XY: 24644 AN XY: 74192

African (AFR) AF: 0.293 AC: 12148 AN: 41406

American (AMR) AF: 0.309 AC: 4707 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.399 AC: 1387 AN: 3472

East Asian (EAS) AF: 0.295 AC: 1522 AN: 5154

South Asian (SAS) AF: 0.347 AC: 1675 AN: 4822

European-Finnish (FIN) AF: 0.391 AC: 4115 AN: 10526

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.348 AC: 23650 AN: 67946

Other (OTH) AF: 0.348 AC: 732 AN: 2106

Alfa AF: 0.268 Hom.: 1290

Bravo AF: 0.321

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.94
DANN	Benign	0.67
PhyloP100		-0.061
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: rs7077242; hg19: chr10-35481965;