rs757349

Variant names:

• chr19-18700066-G-A
• rs757349
• NM_015321.3:c.126+16238G>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.126+16238G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0658 in 152,222 control chromosomes in the GnomAD database, including 494 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 0.066 (494 hom., cov: 33)
• Consequence: CRTC1 NM_015321.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0430
• Publications: 2 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.245 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRTC1	NM_015321.3	MANE Select	c.126+16238G>A		intron	N/A	NP_056136.2
	CRTC1	NM_001098482.2		c.126+16238G>A		intron	N/A	NP_001091952.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRTC1	ENST00000321949.13	TSL:1 MANE Select	c.126+16238G>A		intron	N/A	ENSP00000323332.7
	CRTC1	ENST00000338797.10	TSL:1	c.126+16238G>A		intron	N/A	ENSP00000345001.5

Frequencies

GnomAD3 genomes AF: 0.0658 AC: 10015 AN: 152102 Hom.: 494 Cov.: 33

Gnomad AFR AF: 0.0379

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0569

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.257

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.0361

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0672

Gnomad OTH AF: 0.0694

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0658 AC: 10018 AN: 152222 Hom.: 494 Cov.: 33 AF XY: 0.0671 AC XY: 4991 AN XY: 74424

African (AFR) AF: 0.0379 AC: 1575 AN: 41530

American (AMR) AF: 0.0568 AC: 868 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 417 AN: 3472

East Asian (EAS) AF: 0.257 AC: 1328 AN: 5168

South Asian (SAS) AF: 0.140 AC: 678 AN: 4828

European-Finnish (FIN) AF: 0.0361 AC: 383 AN: 10616

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0672 AC: 4572 AN: 68006

Other (OTH) AF: 0.0697 AC: 147 AN: 2110

Alfa AF: 0.0596 Hom.: 51

Bravo AF: 0.0668

Asia WGS AF: 0.180 AC: 626 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.4
DANN	Benign	0.84
PhyloP100		0.043
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	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: rs757349; hg19: chr19-18810876;