rs10423674

Variant names:

• chr19-18707093-C-A
• rs10423674
• NM_015321.3:c.126+23265C>A

Your query was ambiguous. Multiple possible variants found:

• chr19-18707093-C-A
• chr19-18707093-C-G
• chr19-18707093-C-T

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+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
• Publications: 50 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=-0.72).
• 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 rank	MANE	Protein	UniProt
CRTC1	NM_015321.3	c.126+23265C>A		intron_variant	Intron 1 of 13	ENST00000321949.13	NP_056136.2
CRTC1	NM_001098482.2	c.126+23265C>A		intron_variant	Intron 1 of 14		NP_001091952.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRTC1	ENST00000321949.13	c.126+23265C>A		intron_variant	Intron 1 of 13	1	NM_015321.3	ENSP00000323332.7
CRTC1	ENST00000338797.10	c.126+23265C>A		intron_variant	Intron 1 of 14	1		ENSP00000345001.5

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

African (AFR) AF: 0.530 AC: 21982 AN: 41448

American (AMR) AF: 0.449 AC: 6849 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.225 AC: 779 AN: 3468

East Asian (EAS) AF: 0.642 AC: 3328 AN: 5182

South Asian (SAS) AF: 0.365 AC: 1753 AN: 4808

European-Finnish (FIN) AF: 0.449 AC: 4708 AN: 10492

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.333 AC: 22636 AN: 67966

Other (OTH) AF: 0.391 AC: 825 AN: 2112

Alfa AF: 0.356 Hom.: 41785

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
PhyloP100		0.056
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: rs10423674; hg19: chr19-18817903;