chr1-94901860-C-T

Position:

• chr1-94901860-C-T

Variant summary

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

The NM_001839.5(CNN3):​c.385-75G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0941 in 1,064,266 control chromosomes in the GnomAD database, including 5,249 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 0.091 (701 hom., cov: 32)
  • Exomes 𝑓: 0.095 (4548 hom.)
• Consequence: CNN3 NM_001839.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.871

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNN3	NM_001839.5	c.385-75G>A		intron_variant		ENST00000370206.9	NP_001830.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNN3	ENST00000370206.9	c.385-75G>A		intron_variant		1	NM_001839.5	ENSP00000359225	P1

Frequencies

GnomAD3 genomes AF: 0.0907 AC: 13783 AN: 152022 Hom.: 701 Cov.: 32

Gnomad AFR AF: 0.0688

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.0792

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.0506

Gnomad SAS AF: 0.0518

Gnomad FIN AF: 0.100

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.0995

GnomAD4 exome AF: 0.0947 AC: 86416 AN: 912126 Hom.: 4548 Cov.: 12 AF XY: 0.0939 AC XY: 44313 AN XY: 472054

Gnomad4 AFR exome AF: 0.0651

Gnomad4 AMR exome AF: 0.0621

Gnomad4 ASJ exome AF: 0.125

Gnomad4 EAS exome AF: 0.0515

Gnomad4 SAS exome AF: 0.0588

Gnomad4 FIN exome AF: 0.104

Gnomad4 NFE exome AF: 0.102

Gnomad4 OTH exome AF: 0.0941

GnomAD4 genome AF: 0.0906 AC: 13782 AN: 152140 Hom.: 701 Cov.: 32 AF XY: 0.0889 AC XY: 6609 AN XY: 74368

Gnomad4 AFR AF: 0.0687

Gnomad4 AMR AF: 0.0791

Gnomad4 ASJ AF: 0.124

Gnomad4 EAS AF: 0.0509

Gnomad4 SAS AF: 0.0512

Gnomad4 FIN AF: 0.100

Gnomad4 NFE AF: 0.107

Gnomad4 OTH AF: 0.0990

Alfa AF: 0.105 Hom.: 1135

Bravo AF: 0.0904

Asia WGS AF: 0.0800 AC: 279 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.9
DANN	Benign	0.17

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: rs2275612; hg19: chr1-95367416;