NM_015321.3:c.126+8534T>G

Variant names:

• chr19-18692362-T-G
• rs10419226
• NM_015321.3:c.126+8534T>G

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+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
• Publications: 37 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.891 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+8534T>G		intron	N/A	NP_056136.2	Q6UUV9-1
	CRTC1	NM_001098482.2		c.126+8534T>G		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+8534T>G		intron	N/A	ENSP00000323332.7	Q6UUV9-1
	CRTC1	ENST00000338797.10	TSL:1	c.126+8534T>G		intron	N/A	ENSP00000345001.5	Q6UUV9-2
	CRTC1	ENST00000929718.1		c.126+8534T>G		intron	N/A	ENSP00000599777.1

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

African (AFR) AF: 0.899 AC: 37313 AN: 41516

American (AMR) AF: 0.619 AC: 9442 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.458 AC: 1588 AN: 3464

East Asian (EAS) AF: 0.661 AC: 3413 AN: 5164

South Asian (SAS) AF: 0.547 AC: 2640 AN: 4822

European-Finnish (FIN) AF: 0.691 AC: 7307 AN: 10574

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.549 AC: 37340 AN: 67964

Other (OTH) AF: 0.609 AC: 1283 AN: 2108

Alfa AF: 0.581 Hom.: 93652

Bravo AF: 0.666

Asia WGS AF: 0.654 AC: 2270 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.7
DANN	Benign	0.76
PhyloP100		-0.51
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: rs10419226; hg19: chr19-18803172;