dbSNP rs1057108: CREM:c.598+7633T>G (chr10-35196021-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001267570.2(CREM):c.-42T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 1,607,806 control chromosomes in the GnomAD database, including 96,394 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

Frequency

Genomes: 𝑓 0.34 ( 8660 hom., cov: 32)

Exomes 𝑓: 0.35 ( 87734 hom. )

Consequence

CREM
NM_001267570.2 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.677

Publications

32 publications found

Variant links:

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]

CREM links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

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_001267570.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CREM	NM_183011.2	MANE Select	c.598+7633T>G	intron	N/A	NP_898829.1	Q03060-31
CREM	NM_001267570.2		c.-42T>G	5_prime_UTR	Exon 1 of 4	NP_001254499.1	Q03060-29
CREM	NM_182724.2		c.-42T>G	5_prime_UTR	Exon 1 of 3	NP_874393.1	Q03060-27

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CREM	ENST00000685392.1	MANE Select	c.598+7633T>G	intron	N/A	ENSP00000509489.1	Q03060-31
CREM	ENST00000345491.7	TSL:1	c.598+7633T>G	intron	N/A	ENSP00000265372.5	Q03060-16
CREM	ENST00000354759.7	TSL:1	c.410-5430T>G	intron	N/A	ENSP00000346804.3	Q03060-26

Frequencies

GnomAD3 genomes

AF:

0.336

AC:

51028

AN:

151874

Hom.:

8631

Cov.:

show subpopulations

Gnomad AFR

AF:

0.312

Gnomad AMI

AF:

0.258

Gnomad AMR

AF:

0.310

Gnomad ASJ

AF:

0.399

Gnomad EAS

AF:

0.294

Gnomad SAS

AF:

0.348

Gnomad FIN

AF:

0.389

Gnomad MID

AF:

0.320

Gnomad NFE

AF:

0.348

Gnomad OTH

AF:

0.344

GnomAD2 exomes

AF:

0.338

AC:

84662

AN:

250244

AF XY:

0.341

show subpopulations

Gnomad AFR exome

AF:

0.312

Gnomad AMR exome

AF:

0.275

Gnomad ASJ exome

AF:

0.397

Gnomad EAS exome

AF:

0.287

Gnomad FIN exome

AF:

0.392

Gnomad NFE exome

AF:

0.351

Gnomad OTH exome

AF:

0.347

GnomAD4 exome

AF:

0.346

AC:

503357

AN:

1455814

Hom.:

87734

Cov.:

AF XY:

0.347

AC XY:

251203

AN XY:

724588

show subpopulations

African (AFR)

AF:

0.318

AC:

10606

AN:

33358

American (AMR)

AF:

0.283

AC:

12628

AN:

44644

Ashkenazi Jewish (ASJ)

AF:

0.391

AC:

10213

AN:

26102

East Asian (EAS)

AF:

0.266

AC:

10530

AN:

39636

South Asian (SAS)

AF:

0.347

AC:

29878

AN:

86086

European-Finnish (FIN)

AF:

0.385

AC:

20495

AN:

53200

Middle Eastern (MID)

AF:

0.337

AC:

1939

AN:

5762

European-Non Finnish (NFE)

AF:

0.349

AC:

386013

AN:

1106858

Other (OTH)

AF:

0.350

AC:

21055

AN:

60168

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

16075

32149

48224

64298

80373

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12280

24560

36840

49120

61400

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.336

AC:

51120

AN:

151992

Hom.:

8660

Cov.:

AF XY:

0.337

AC XY:

25042

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.313

AC:

12961

AN:

41444

American (AMR)

AF:

0.310

AC:

4736

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.399

AC:

1387

AN:

3472

East Asian (EAS)

AF:

0.294

AC:

1522

AN:

5174

South Asian (SAS)

AF:

0.350

AC:

1686

AN:

4824

European-Finnish (FIN)

AF:

0.389

AC:

4101

AN:

10544

Middle Eastern (MID)

AF:

0.316

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.348

AC:

23660

AN:

67966

Other (OTH)

AF:

0.351

AC:

739

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1741

3482

5222

6963

8704

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

510

1020

1530

2040

2550

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.345

Hom.:

13230

Bravo

AF:

0.328

Asia WGS

AF:

0.356

AC:

1236

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

(source)

DANN

Benign

0.70

PhyloP100

0.68

PromoterAI

0.031

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over