rs860873

Variant names:

• chr1-94921652-G-A
• rs860873
• NM_001839.5:c.57+5186C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CNN3	NM_001839.5	c.57+5186C>T		intron_variant	Intron 1 of 6	ENST00000370206.9	NP_001830.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNN3	ENST00000370206.9	c.57+5186C>T		intron_variant	Intron 1 of 6	1	NM_001839.5	ENSP00000359225.4

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

African (AFR) AF: 0.288 AC: 11918 AN: 41394

American (AMR) AF: 0.385 AC: 5889 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.447 AC: 1550 AN: 3466

East Asian (EAS) AF: 0.154 AC: 797 AN: 5160

South Asian (SAS) AF: 0.400 AC: 1928 AN: 4814

European-Finnish (FIN) AF: 0.527 AC: 5566 AN: 10554

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.436 AC: 29643 AN: 67956

Other (OTH) AF: 0.372 AC: 785 AN: 2108

Alfa AF: 0.410 Hom.: 32942

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
PhyloP100		-0.16
Mutation Taster		=99/1	polymorphism (auto)

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: rs860873; hg19: chr1-95387208;