rs10038

Variant names:

• chr19-18781918-C-A
• rs10038
• NM_015321.3:c.*4536C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 23 publications found

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

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015321.3. 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
	CRTC1	NM_015321.3	MANE Select	c.*4536C>A		3_prime_UTR	Exon 14 of 14	NP_056136.2
	CRTC1	NM_001098482.2		c.*4536C>A		3_prime_UTR	Exon 15 of 15	NP_001091952.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRTC1	ENST00000321949.13	TSL:1 MANE Select	c.*4536C>A		3_prime_UTR	Exon 14 of 14	ENSP00000323332.7
	CRTC1	ENST00000338797.10	TSL:1	c.*4536C>A		3_prime_UTR	Exon 15 of 15	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

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: 27 AN: 70

Middle Eastern (MID) AF: 0.170 AC: 82 AN: 482

European-Non Finnish (NFE) AF: 0.302 AC: 14559 AN: 48230

Other (OTH) AF: 0.277 AC: 1806 AN: 6528

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

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: 54 AN: 292

European-Non Finnish (NFE) AF: 0.324 AC: 22035 AN: 67968

Other (OTH) AF: 0.240 AC: 507 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.0
DANN	Benign	0.88
PhyloP100		-0.38
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs10038; hg19: chr19-18892728;