10-35150261-T-C

Position:

• chr10-35150261-T-C

Variant summary

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

The NM_183011.2(CREM):​c.168+1770T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 152,018 control chromosomes in the GnomAD database, including 1,592 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 0.14 (1592 hom., cov: 31)
• Consequence: CREM NM_183011.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.873

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CREM	NM_183011.2	c.168+1770T>C		intron_variant		ENST00000685392.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CREM	ENST00000685392.1	c.168+1770T>C		intron_variant			NM_183011.2	A1

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20580 AN: 151898 Hom.: 1589 Cov.: 31

Gnomad AFR AF: 0.0630

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.0580

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.147

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

GnomAD4 genome AF: 0.136 AC: 20603 AN: 152018 Hom.: 1592 Cov.: 31 AF XY: 0.136 AC XY: 10136 AN XY: 74320

Gnomad4 AFR AF: 0.0633

Gnomad4 AMR AF: 0.118

Gnomad4 ASJ AF: 0.247

Gnomad4 EAS AF: 0.0581

Gnomad4 SAS AF: 0.199

Gnomad4 FIN AF: 0.179

Gnomad4 NFE AF: 0.172

Gnomad4 OTH AF: 0.146

Alfa AF: 0.142 Hom.: 203

Bravo AF: 0.126

Asia WGS AF: 0.113 AC: 394 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.97
DANN	Benign	0.25

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs877779; hg19: chr10-35439189;