19-18692362-T-G

Variant summary

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

The NM_015321.3(CRTC1):c.126+8534T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.664 in 152,068 control chromosomes in the GnomAD database, including 35,356 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 0.66 (35356 hom., cov: 31)
• Consequence: CRTC1 NM_015321.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.506

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.891 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRTC1	NM_015321.3	c.126+8534T>G		intron_variant		ENST00000321949.13
CRTC1	NM_001098482.2	c.126+8534T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRTC1	ENST00000321949.13	c.126+8534T>G		intron_variant		1	NM_015321.3	A1
CRTC1	ENST00000338797.10	c.126+8534T>G		intron_variant		1		P4

Frequencies

GnomAD3 genomes AF: 0.664 AC: 100837 AN: 151950 Hom.: 35290 Cov.: 31

Gnomad AFR AF: 0.899

Gnomad AMI AF: 0.545

Gnomad AMR AF: 0.619

Gnomad ASJ AF: 0.458

Gnomad EAS AF: 0.661

Gnomad SAS AF: 0.548

Gnomad FIN AF: 0.691

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.549

Gnomad OTH AF: 0.605

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

GnomAD4 genome AF: 0.664 AC: 100961 AN: 152068 Hom.: 35356 Cov.: 31 AF XY: 0.666 AC XY: 49480 AN XY: 74308

Gnomad4 AFR AF: 0.899

Gnomad4 AMR AF: 0.619

Gnomad4 ASJ AF: 0.458

Gnomad4 EAS AF: 0.661

Gnomad4 SAS AF: 0.547

Gnomad4 FIN AF: 0.691

Gnomad4 NFE AF: 0.549

Gnomad4 OTH AF: 0.609

Alfa AF: 0.559 Hom.: 30293

Bravo AF: 0.666

Asia WGS AF: 0.654 AC: 2270 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	1.7
Dann	Benign	0.76

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: rs10419226; hg19: chr19-18803172;