dbSNP rs10038: CRTC1:c.*4536C>A (chr19-18781918-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_015321.3(CRTC1):c.*4536C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 230,316 control chromosomes in the GnomAD database, including 9,345 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 0.28 ( 6426 hom., cov: 33)

Exomes 𝑓: 0.26 ( 2919 hom. )

Consequence

CRTC1
NM_015321.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.376

Publications

23 publications found

Variant links:

Genes affected

CRTC1 (HGNC:16062): (CREB regulated transcription coactivator 1) Enables cAMP response element binding protein binding activity. Involved in positive regulation of transcription by RNA polymerase II. Located in cytosol; nuclear body; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

CRTC1 links:

Genome browser will be placed here

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=-0.77).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRTC1	NM_015321.3 link	c.*4536C>A		3_prime_UTR_variant	Exon 14 of 14	ENST00000321949.13	NP_056136.2	Q6UUV9-1
CRTC1	NM_001098482.2 link	c.*4536C>A		3_prime_UTR_variant	Exon 15 of 15		NP_001091952.1	Q6UUV9-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRTC1	ENST00000321949.13 link	c.*4536C>A		3_prime_UTR_variant	Exon 14 of 14	1	NM_015321.3	ENSP00000323332.7		Q6UUV9-1
CRTC1	ENST00000338797.10 link	c.*4536C>A		3_prime_UTR_variant	Exon 15 of 15	1		ENSP00000345001.5		Q6UUV9-2

Frequencies

GnomAD3 genomes

AF:

0.282

AC:

42943

AN:

152044

Hom.:

6428

Cov.:

show subpopulations

Gnomad AFR

AF:

0.244

Gnomad AMI

AF:

0.212

Gnomad AMR

AF:

0.247

Gnomad ASJ

AF:

0.240

Gnomad EAS

AF:

0.0980

Gnomad SAS

AF:

0.142

Gnomad FIN

AF:

0.401

Gnomad MID

AF:

0.194

Gnomad NFE

AF:

0.324

Gnomad OTH

AF:

0.243

GnomAD4 exome

AF:

0.259

AC:

20238

AN:

78154

Hom.:

2919

Cov.:

AF XY:

0.257

AC XY:

9259

AN XY:

36000

show subpopulations

African (AFR)

AF:

0.243

AC:

899

AN:

3700

American (AMR)

AF:

0.239

AC:

573

AN:

2394

Ashkenazi Jewish (ASJ)

AF:

0.249

AC:

1230

AN:

4944

East Asian (EAS)

AF:

0.0864

AC:

962

AN:

11130

South Asian (SAS)

AF:

0.148

AC:

100

AN:

676

European-Finnish (FIN)

AF:

0.386

AC:

AN:

Middle Eastern (MID)

AF:

0.170

AC:

AN:

482

European-Non Finnish (NFE)

AF:

0.302

AC:

14559

AN:

48230

Other (OTH)

AF:

0.277

AC:

1806

AN:

6528

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

745

1490

2234

2979

3724

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

160

200

<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:

0.282

AC:

42943

AN:

152162

Hom.:

6426

Cov.:

AF XY:

0.281

AC XY:

20862

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.244

AC:

10109

AN:

41512

American (AMR)

AF:

0.247

AC:

3783

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.240

AC:

831

AN:

3466

East Asian (EAS)

AF:

0.0980

AC:

507

AN:

5172

South Asian (SAS)

AF:

0.141

AC:

682

AN:

4828

European-Finnish (FIN)

AF:

0.401

AC:

4242

AN:

10590

Middle Eastern (MID)

AF:

0.185

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.324

AC:

22035

AN:

67968

Other (OTH)

AF:

0.240

AC:

507

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1622

3244

4866

6488

8110

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

436

872

1308

1744

2180

<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:

0.301

Hom.:

26890

Bravo

AF:

0.267

Asia WGS

AF:

0.132

AC:

460

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

3.0

(source)

DANN

Benign

0.88

PhyloP100

-0.38

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over