chr19-11544195-A-T

Position:

• chr19-11544195-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001299.6(CNN1):​c.186-2480A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0452 in 151,942 control chromosomes in the GnomAD database, including 191 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 0.045 (191 hom., cov: 30)
• Consequence: CNN1 NM_001299.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0850

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0903 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNN1	NM_001299.6	c.186-2480A>T		intron_variant		ENST00000252456.7	NP_001290.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNN1	ENST00000252456.7	c.186-2480A>T		intron_variant		1	NM_001299.6	ENSP00000252456.1

Frequencies

GnomAD3 genomes AF: 0.0451 AC: 6853 AN: 151824 Hom.: 191 Cov.: 30

Gnomad AFR AF: 0.0659

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0331

Gnomad ASJ AF: 0.0265

Gnomad EAS AF: 0.0973

Gnomad SAS AF: 0.0975

Gnomad FIN AF: 0.0392

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0300

Gnomad OTH AF: 0.0442

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

GnomAD4 genome AF: 0.0452 AC: 6868 AN: 151942 Hom.: 191 Cov.: 30 AF XY: 0.0460 AC XY: 3419 AN XY: 74256

Gnomad4 AFR AF: 0.0661

Gnomad4 AMR AF: 0.0330

Gnomad4 ASJ AF: 0.0265

Gnomad4 EAS AF: 0.0973

Gnomad4 SAS AF: 0.0973

Gnomad4 FIN AF: 0.0392

Gnomad4 NFE AF: 0.0299

Gnomad4 OTH AF: 0.0452

Alfa AF: 0.0128 Hom.: 4

Bravo AF: 0.0456

Asia WGS AF: 0.103 AC: 357 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.0
DANN	Benign	0.32

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

Other links and lift over

dbSNP: rs11880637; hg19: chr19-11655010;