rs860873

chr1-94921652-G-A

Variant summary

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

The NM_001839.5(CNN3):c.57+5186C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 151,936 control chromosomes in the GnomAD database, including 11,787 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 0.38 (11787 hom., cov: 32)
• Consequence: CNN3 NM_001839.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.158

Genes affected

CNN3 (HGNC:2157): (calponin 3) This gene encodes a protein with a markedly acidic C terminus; the basic N-terminus is highly homologous to the N-terminus of a related gene, CNN1. Members of the CNN gene family all contain similar tandemly repeated motifs. This encoded protein is associated with the cytoskeleton but is not involved in contraction. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNN3	NM_001839.5	c.57+5186C>T		intron_variant		ENST00000370206.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNN3	ENST00000370206.9	c.57+5186C>T		intron_variant		1	NM_001839.5	P1

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58402 AN: 151818 Hom.: 11777 Cov.: 32

Gnomad AFR AF: 0.288

Gnomad AMI AF: 0.255

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.401

Gnomad FIN AF: 0.527

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.436

Gnomad OTH AF: 0.370

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

GnomAD4 genome AF: 0.385 AC: 58445 AN: 151936 Hom.: 11787 Cov.: 32 AF XY: 0.387 AC XY: 28738 AN XY: 74250

Gnomad4 AFR AF: 0.288

Gnomad4 AMR AF: 0.385

Gnomad4 ASJ AF: 0.447

Gnomad4 EAS AF: 0.154

Gnomad4 SAS AF: 0.400

Gnomad4 FIN AF: 0.527

Gnomad4 NFE AF: 0.436

Gnomad4 OTH AF: 0.372

Alfa AF: 0.423 Hom.: 11052

Bravo AF: 0.368

Asia WGS AF: 0.270 AC: 941 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.2
Dann	Benign	0.70

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: rs860873; hg19: chr1-95387208;