19-18698105-T-A

Variant names:

• chr19-18698105-T-A
• rs7258722
• NM_015321.3:c.126+14277T>A

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+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
• Publications: 8 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=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.842 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015321.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRTC1	NM_015321.3	MANE Select	c.126+14277T>A		intron	N/A	NP_056136.2	Q6UUV9-1
	CRTC1	NM_001098482.2		c.126+14277T>A		intron	N/A	NP_001091952.1	Q6UUV9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRTC1	ENST00000321949.13	TSL:1 MANE Select	c.126+14277T>A		intron	N/A	ENSP00000323332.7	Q6UUV9-1
	CRTC1	ENST00000338797.10	TSL:1	c.126+14277T>A		intron	N/A	ENSP00000345001.5	Q6UUV9-2
	CRTC1	ENST00000929718.1		c.126+14277T>A		intron	N/A	ENSP00000599777.1

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

African (AFR) AF: 0.727 AC: 30082 AN: 41392

American (AMR) AF: 0.495 AC: 7550 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.343 AC: 1186 AN: 3462

East Asian (EAS) AF: 0.863 AC: 4442 AN: 5148

South Asian (SAS) AF: 0.498 AC: 2384 AN: 4786

European-Finnish (FIN) AF: 0.465 AC: 4895 AN: 10530

Middle Eastern (MID) AF: 0.330 AC: 91 AN: 276

European-Non Finnish (NFE) AF: 0.399 AC: 27027 AN: 67738

Other (OTH) AF: 0.490 AC: 1032 AN: 2108

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	1.4
DANN	Benign	0.70
PhyloP100		-2.4
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: rs7258722; hg19: chr19-18808915;