chr19-18698105-T-A

Position:

• chr19-18698105-T-A

Variant summary

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

The NM_015321.3(CRTC1):​c.126+14277T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 151,592 control chromosomes in the GnomAD database, including 22,501 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 0.52 (22501 hom., cov: 33)
• Consequence: CRTC1 NM_015321.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.38

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=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.842 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRTC1	NM_015321.3	c.126+14277T>A		intron_variant		ENST00000321949.13
CRTC1	NM_001098482.2	c.126+14277T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRTC1	ENST00000321949.13	c.126+14277T>A		intron_variant		1	NM_015321.3	A1
CRTC1	ENST00000338797.10	c.126+14277T>A		intron_variant		1		P4

Frequencies

GnomAD3 genomes AF: 0.522 AC: 78993 AN: 151470 Hom.: 22439 Cov.: 33

Gnomad AFR AF: 0.726

Gnomad AMI AF: 0.482

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.343

Gnomad EAS AF: 0.863

Gnomad SAS AF: 0.498

Gnomad FIN AF: 0.465

Gnomad MID AF: 0.333

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.483

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

GnomAD4 genome AF: 0.522 AC: 79123 AN: 151592 Hom.: 22501 Cov.: 33 AF XY: 0.523 AC XY: 38751 AN XY: 74098

Gnomad4 AFR AF: 0.727

Gnomad4 AMR AF: 0.495

Gnomad4 ASJ AF: 0.343

Gnomad4 EAS AF: 0.863

Gnomad4 SAS AF: 0.498

Gnomad4 FIN AF: 0.465

Gnomad4 NFE AF: 0.399

Gnomad4 OTH AF: 0.490

Alfa AF: 0.310 Hom.: 757

Bravo AF: 0.535

Asia WGS AF: 0.710 AC: 2467 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	1.4
DANN	Benign	0.70

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: rs7258722; hg19: chr19-18808915;