rs11672633

Variant names:

• chr19-11548829-G-C
• rs11672633
• NM_001299.6:c.502-494G>C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001299.6(CNN1):​c.502-494G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00424 in 151,792 control chromosomes in the GnomAD database, including 1 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 0.0042 (1 hom., cov: 33)
• Consequence: CNN1 NM_001299.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.718
• Publications: 1 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BS2: High AC in GnomAd4 at 643 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNN1	NM_001299.6	MANE Select	c.502-494G>C		intron	N/A	NP_001290.2
	CNN1	NM_001308341.2		c.352-494G>C		intron	N/A	NP_001295270.1	B7Z7E1
	CNN1	NM_001308342.2		c.352-494G>C		intron	N/A	NP_001295271.1	B7Z7E1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNN1	ENST00000252456.7	TSL:1 MANE Select	c.502-494G>C		intron	N/A	ENSP00000252456.1	P51911-1
	CNN1	ENST00000873893.1		c.496-494G>C		intron	N/A	ENSP00000543952.1
	CNN1	ENST00000962387.1		c.496-494G>C		intron	N/A	ENSP00000632446.1

Frequencies

GnomAD3 genomes AF: 0.00424 AC: 643 AN: 151674 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00107

Gnomad AMI AF: 0.00659

Gnomad AMR AF: 0.00408

Gnomad ASJ AF: 0.00432

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00275

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00707

Gnomad OTH AF: 0.00288

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

GnomAD4 genome AF: 0.00424 AC: 643 AN: 151792 Hom.: 1 Cov.: 33 AF XY: 0.00402 AC XY: 298 AN XY: 74194

African (AFR) AF: 0.00106 AC: 44 AN: 41370

American (AMR) AF: 0.00407 AC: 62 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.00432 AC: 15 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5148

South Asian (SAS) AF: 0.000209 AC: 1 AN: 4794

European-Finnish (FIN) AF: 0.00275 AC: 29 AN: 10562

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

European-Non Finnish (NFE) AF: 0.00707 AC: 480 AN: 67922

Other (OTH) AF: 0.00285 AC: 6 AN: 2106

Alfa AF: 0.00503 Hom.: 0

Bravo AF: 0.00429

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.55
DANN	Benign	0.58
PhyloP100		0.72

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: rs11672633; hg19: chr19-11659644;