NM_183011.2:c.312G>A

Variant names:

• chr10-35179179-G-A
• rs11010115
• NM_183011.2:c.312G>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_183011.2(CREM):​c.312G>A​(p.Lys104Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.006 in 1,613,922 control chromosomes in the GnomAD database, including 442 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.030 (224 hom., cov: 33)
  • Exomes 𝑓: 0.0035 (218 hom.)
• Consequence: CREM NM_183011.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.17
• Publications: 2 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 10-35179179-G-A is Benign according to our data. Variant chr10-35179179-G-A is described in ClinVar as Benign. ClinVar VariationId is 776507.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.17 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.101 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.312G>A	p.Lys104Lys	synonymous	Exon 5 of 8	NP_898829.1	Q03060-31
	CREM	NM_001394595.1		c.312G>A	p.Lys104Lys	synonymous	Exon 5 of 8	NP_001381524.1	Q03060-16
	CREM	NM_181571.3		c.312G>A	p.Lys104Lys	synonymous	Exon 5 of 8	NP_853549.1	Q03060-16

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CREM	ENST00000685392.1	MANE Select	c.312G>A	p.Lys104Lys	synonymous	Exon 5 of 8	ENSP00000509489.1	Q03060-31
	CREM	ENST00000345491.7	TSL:1	c.312G>A	p.Lys104Lys	synonymous	Exon 5 of 8	ENSP00000265372.5	Q03060-16
	CREM	ENST00000354759.7	TSL:1	c.312G>A	p.Lys104Lys	synonymous	Exon 5 of 8	ENSP00000346804.3	Q03060-26

Frequencies

GnomAD3 genomes AF: 0.0297 AC: 4519 AN: 152160 Hom.: 222 Cov.: 33

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00864

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000779

Gnomad OTH AF: 0.0158

GnomAD2 exomes AF: 0.00785 AC: 1972 AN: 251136 AF XY: 0.00559

Gnomad AFR exome AF: 0.107

Gnomad AMR exome AF: 0.00437

Gnomad ASJ exome AF: 0.000398

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000458

Gnomad OTH exome AF: 0.00424

GnomAD4 exome AF: 0.00352 AC: 5149 AN: 1461644 Hom.: 218 Cov.: 31 AF XY: 0.00305 AC XY: 2217 AN XY: 727110

African (AFR) AF: 0.113 AC: 3779 AN: 33468

American (AMR) AF: 0.00503 AC: 225 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.000537 AC: 14 AN: 26094

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39680

South Asian (SAS) AF: 0.000313 AC: 27 AN: 86222

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53412

Middle Eastern (MID) AF: 0.00884 AC: 51 AN: 5766

European-Non Finnish (NFE) AF: 0.000566 AC: 629 AN: 1111906

Other (OTH) AF: 0.00699 AC: 422 AN: 60388

GnomAD4 genome AF: 0.0298 AC: 4536 AN: 152278 Hom.: 224 Cov.: 33 AF XY: 0.0290 AC XY: 2160 AN XY: 74452

African (AFR) AF: 0.104 AC: 4313 AN: 41522

American (AMR) AF: 0.00863 AC: 132 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.000779 AC: 53 AN: 68032

Other (OTH) AF: 0.0156 AC: 33 AN: 2112

Alfa AF: 0.0162 Hom.: 58

Bravo AF: 0.0334

Asia WGS AF: 0.00462 AC: 17 AN: 3478

EpiCase AF: 0.000709

EpiControl AF: 0.000356

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	8.9
DANN	Benign	0.65
PhyloP100		2.2
PromoterAI		-0.018	Neutral
Mutation Taster		=70/30	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: rs11010115; hg19: chr10-35468107; COSMIC: COSV59769023;