rs757349

Positions:

• chr19-18700066-G-A

Variant summary

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

The ENST00000321949.13(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 ENST00000321949.13 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0430

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRTC1	NM_015321.3	c.126+16238G>A		intron_variant		ENST00000321949.13	NP_056136.2
CRTC1	NM_001098482.2	c.126+16238G>A		intron_variant			NP_001091952.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRTC1	ENST00000321949.13	c.126+16238G>A		intron_variant		1	NM_015321.3	ENSP00000323332	A1
CRTC1	ENST00000338797.10	c.126+16238G>A		intron_variant		1		ENSP00000345001	P4

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

Gnomad4 AFR AF: 0.0379

Gnomad4 AMR AF: 0.0568

Gnomad4 ASJ AF: 0.120

Gnomad4 EAS AF: 0.257

Gnomad4 SAS AF: 0.140

Gnomad4 FIN AF: 0.0361

Gnomad4 NFE AF: 0.0672

Gnomad4 OTH AF: 0.0697

Alfa AF: 0.0604 Hom.: 51

Bravo AF: 0.0668

Asia WGS AF: 0.180 AC: 626 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.4
DANN	Benign	0.84
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

LitVar

Other links and lift over

dbSNP: rs757349; hg19: chr19-18810876;