19-11544195-A-C

Variant names:

• chr19-11544195-A-C
• rs11880637
• NM_001299.6:c.186-2480A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001299.6(CNN1):​c.186-2480A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 30)
• Consequence: CNN1 NM_001299.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0850
• Publications: 8 publications found

Genes affected

CNN1 (HGNC:2155): (calponin 1) Predicted to enable actin binding activity. Involved in negative regulation of vascular associated smooth muscle cell proliferation. Located in cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001299.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNN1	NM_001299.6	MANE Select	c.186-2480A>C		intron	N/A	NP_001290.2
	CNN1	NM_001308341.2		c.36-2480A>C		intron	N/A	NP_001295270.1
	CNN1	NM_001308342.2		c.36-2480A>C		intron	N/A	NP_001295271.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNN1	ENST00000252456.7	TSL:1 MANE Select	c.186-2480A>C		intron	N/A	ENSP00000252456.1
	CNN1	ENST00000535659.6	TSL:2	c.36-2480A>C		intron	N/A	ENSP00000442031.1
	CNN1	ENST00000592923.5	TSL:2	c.36-2480A>C		intron	N/A	ENSP00000468259.1

Frequencies

GnomAD3 genomes Cov.: 30

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

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 4

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.1
DANN	Benign	0.24
PhyloP100		0.085

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: rs11880637; hg19: chr19-11655010;