rs10423674

chr19-18707093-C-Achr19-18707093-C-Gchr19-18707093-C-T

Variant summary

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

The NM_015321.3(CRTC1):c.126+23265C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 151,940 control chromosomes in the GnomAD database, including 14,059 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 0.42 (14059 hom., cov: 32)
• Consequence: CRTC1 NM_015321.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0560

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=-0.72).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRTC1	NM_015321.3	c.126+23265C>A		intron_variant		ENST00000321949.13
CRTC1	NM_001098482.2	c.126+23265C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRTC1	ENST00000321949.13	c.126+23265C>A		intron_variant		1	NM_015321.3	A1
CRTC1	ENST00000338797.10	c.126+23265C>A		intron_variant		1		P4

Frequencies

GnomAD3 genomes AF: 0.416 AC: 63233 AN: 151822 Hom.: 14018 Cov.: 32

Gnomad AFR AF: 0.530

Gnomad AMI AF: 0.443

Gnomad AMR AF: 0.448

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.642

Gnomad SAS AF: 0.364

Gnomad FIN AF: 0.449

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.384

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

GnomAD4 genome AF: 0.417 AC: 63325 AN: 151940 Hom.: 14059 Cov.: 32 AF XY: 0.421 AC XY: 31300 AN XY: 74276

Gnomad4 AFR AF: 0.530

Gnomad4 AMR AF: 0.449

Gnomad4 ASJ AF: 0.225

Gnomad4 EAS AF: 0.642

Gnomad4 SAS AF: 0.365

Gnomad4 FIN AF: 0.449

Gnomad4 NFE AF: 0.333

Gnomad4 OTH AF: 0.391

Alfa AF: 0.336 Hom.: 15914

Bravo AF: 0.423

Asia WGS AF: 0.535 AC: 1856 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
Cadd	Benign	14
Dann	Benign	0.88

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: rs10423674; hg19: chr19-18817903;