rs10038

Positions:

• chr19-18781918-C-A

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.376

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
CRTC1	NM_015321.3	c.*4536C>A		3_prime_UTR_variant	14/14	ENST00000321949.13	NP_056136.2
CRTC1	NM_001098482.2	c.*4536C>A		3_prime_UTR_variant	15/15		NP_001091952.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRTC1	ENST00000321949.13	c.*4536C>A		3_prime_UTR_variant	14/14	1	NM_015321.3	ENSP00000323332.7
CRTC1	ENST00000338797.10	c.*4536C>A		3_prime_UTR_variant	15/15	1		ENSP00000345001.5

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42943 AN: 152044 Hom.: 6428 Cov.: 33

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.: 0 AF XY: 0.257 AC XY: 9259 AN XY: 36000

Gnomad4 AFR exome AF: 0.243

Gnomad4 AMR exome AF: 0.239

Gnomad4 ASJ exome AF: 0.249

Gnomad4 EAS exome AF: 0.0864

Gnomad4 SAS exome AF: 0.148

Gnomad4 FIN exome AF: 0.386

Gnomad4 NFE exome AF: 0.302

Gnomad4 OTH exome AF: 0.277

GnomAD4 genome AF: 0.282 AC: 42943 AN: 152162 Hom.: 6426 Cov.: 33 AF XY: 0.281 AC XY: 20862 AN XY: 74374

Gnomad4 AFR AF: 0.244

Gnomad4 AMR AF: 0.247

Gnomad4 ASJ AF: 0.240

Gnomad4 EAS AF: 0.0980

Gnomad4 SAS AF: 0.141

Gnomad4 FIN AF: 0.401

Gnomad4 NFE AF: 0.324

Gnomad4 OTH AF: 0.240

Alfa AF: 0.302 Hom.: 11337

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
DANN	Benign	0.88

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10038; hg19: chr19-18892728;