rs140269231

Variant names:

• chr19-18753490-A-G
• rs140269231
• NM_015321.3:c.539-10A>G

Your query was ambiguous. Multiple possible variants found:

• chr19-18753490-A-G
• chr19-18753490-A-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_015321.3(CRTC1):​c.539-10A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00138 in 1,594,552 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0073 (11 hom., cov: 31)
  • Exomes 𝑓: 0.00075 (17 hom.)
• Consequence: CRTC1 NM_015321.3 intron
• Scores: Splicing: ADA: 0.00004676
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.29
• Publications: 1 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 19-18753490-A-G is Benign according to our data. Variant chr19-18753490-A-G is described in ClinVar as Benign. ClinVar VariationId is 788814.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00733 (1108/151062) while in subpopulation AFR AF = 0.0258 (1060/41034). AF 95% confidence interval is 0.0245. There are 11 homozygotes in GnomAd4. There are 520 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1108 AD gene.

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.539-10A>G		intron	N/A	NP_056136.2	Q6UUV9-1
	CRTC1	NM_001098482.2		c.587-10A>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.539-10A>G		intron	N/A	ENSP00000323332.7	Q6UUV9-1
	CRTC1	ENST00000338797.10	TSL:1	c.587-10A>G		intron	N/A	ENSP00000345001.5	Q6UUV9-2
	CRTC1	ENST00000594658.5	TSL:1	c.416-10A>G		intron	N/A	ENSP00000468893.1	M0QX46

Frequencies

GnomAD3 genomes AF: 0.00734 AC: 1108 AN: 150942 Hom.: 11 Cov.: 31

Gnomad AFR AF: 0.0259

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00238

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000737

Gnomad OTH AF: 0.00339

GnomAD2 exomes AF: 0.00182 AC: 434 AN: 238692 AF XY: 0.00121

Gnomad AFR exome AF: 0.0252

Gnomad AMR exome AF: 0.000744

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000363

Gnomad OTH exome AF: 0.000859

GnomAD4 exome AF: 0.000752 AC: 1085 AN: 1443490 Hom.: 17 Cov.: 28 AF XY: 0.000629 AC XY: 452 AN XY: 718388

African (AFR) AF: 0.0272 AC: 882 AN: 32370

American (AMR) AF: 0.00111 AC: 46 AN: 41520

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25622

East Asian (EAS) AF: 0.00 AC: 0 AN: 39532

South Asian (SAS) AF: 0.0000717 AC: 6 AN: 83700

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53268

Middle Eastern (MID) AF: 0.00141 AC: 8 AN: 5676

European-Non Finnish (NFE) AF: 0.0000236 AC: 26 AN: 1102104

Other (OTH) AF: 0.00196 AC: 117 AN: 59698

GnomAD4 genome AF: 0.00733 AC: 1108 AN: 151062 Hom.: 11 Cov.: 31 AF XY: 0.00706 AC XY: 520 AN XY: 73696

African (AFR) AF: 0.0258 AC: 1060 AN: 41034

American (AMR) AF: 0.00238 AC: 36 AN: 15148

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3460

East Asian (EAS) AF: 0.00 AC: 0 AN: 5146

South Asian (SAS) AF: 0.00 AC: 0 AN: 4770

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000737 AC: 5 AN: 67806

Other (OTH) AF: 0.00335 AC: 7 AN: 2088

Alfa AF: 0.00542 Hom.: 3

Bravo AF: 0.00849

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.32
DANN	Benign	0.31
PhyloP100		-2.3
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000047
dbscSNV1_RF	Benign	0.010
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: rs140269231; hg19: chr19-18864300;