Variant 19-11549385-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_001299.6(CNN1):c.564C>T(p.Leu188=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000988 in 1,614,046 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00098 ( 4 hom. )

Consequence

CNN1
NM_001299.6 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.112

Variant links:

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]

CNN1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP6

Variant 19-11549385-C-T is Benign according to our data. Variant chr19-11549385-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2649335.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.112 with no splicing effect.

BS2

High AC in GnomAd4 at 160 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNN1	NM_001299.6 linkuse as main transcript	c.564C>T	p.Leu188=	synonymous_variant	6/7	ENST00000252456.7	NP_001290.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNN1	ENST00000252456.7 linkuse as main transcript	c.564C>T	p.Leu188=	synonymous_variant	6/7	1	NM_001299.6	ENSP00000252456	P1	P51911-1

Frequencies

GnomAD3 genomes

AF:

0.00105

AC:

160

AN:

152076

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000266

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00328

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.00131

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000959

AC:

241

AN:

251408

Hom.:

AF XY:

0.00102

AC XY:

138

AN XY:

135896

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.00119

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00114

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.00125

Gnomad OTH exome

AF:

0.00261

GnomAD4 exome

AF:

0.000981

AC:

1434

AN:

1461852

Hom.:

Cov.:

AF XY:

0.000986

AC XY:

717

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.00134

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00136

Gnomad4 FIN exome

AF:

0.000300

Gnomad4 NFE exome

AF:

0.000998

Gnomad4 OTH exome

AF:

0.000960

GnomAD4 genome

AF:

0.00105

AC:

160

AN:

152194

Hom.:

Cov.:

AF XY:

0.00112

AC XY:

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.00327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00131

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000873

Hom.:

Bravo

AF:

0.00118

EpiCase

AF:

0.00109

EpiControl

AF:

0.00142

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2022

CNN1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

7.8

DANN

Benign

0.83

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over