chr1-94901860-C-T

Variant names:

• chr1-94901860-C-T
• rs2275612
• NM_001839.5:c.385-75G>A

Variant summary

Our verdict is Benign. The variant received -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
• 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=-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 rank	MANE	Protein	UniProt
CNN3	NM_001839.5	c.385-75G>A		intron_variant	Intron 4 of 6	ENST00000370206.9	NP_001830.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNN3	ENST00000370206.9	c.385-75G>A		intron_variant	Intron 4 of 6	1	NM_001839.5	ENSP00000359225.4

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

African (AFR) AF: 0.0651 AC: 1408 AN: 21630

American (AMR) AF: 0.0621 AC: 2099 AN: 33816

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 2572 AN: 20622

East Asian (EAS) AF: 0.0515 AC: 1879 AN: 36460

South Asian (SAS) AF: 0.0588 AC: 3996 AN: 67946

European-Finnish (FIN) AF: 0.104 AC: 5138 AN: 49608

Middle Eastern (MID) AF: 0.129 AC: 590 AN: 4588

European-Non Finnish (NFE) AF: 0.102 AC: 64789 AN: 635542

Other (OTH) AF: 0.0941 AC: 3945 AN: 41914

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

African (AFR) AF: 0.0687 AC: 2850 AN: 41512

American (AMR) AF: 0.0791 AC: 1208 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 432 AN: 3470

East Asian (EAS) AF: 0.0509 AC: 264 AN: 5190

South Asian (SAS) AF: 0.0512 AC: 246 AN: 4800

European-Finnish (FIN) AF: 0.100 AC: 1060 AN: 10584

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.107 AC: 7245 AN: 67992

Other (OTH) AF: 0.0990 AC: 209 AN: 2112

Alfa AF: 0.104 Hom.: 1475

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
PhyloP100		-0.87
Mutation Taster		=100/0	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: rs2275612; hg19: chr1-95367416;