rs2275612

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr1-94901860-C-A
• chr1-94901860-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001839.5(CNN3):​c.385-75G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000011 in 912,892 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000011 (0 hom.)
• Consequence: CNN3 NM_001839.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.871
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001839.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNN3	NM_001839.5	MANE Select	c.385-75G>T		intron	N/A	NP_001830.1
	CNN3	NM_001286056.2		c.262-75G>T		intron	N/A	NP_001272985.1
	CNN3	NM_001286055.2		c.247-75G>T		intron	N/A	NP_001272984.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNN3	ENST00000370206.9	TSL:1 MANE Select	c.385-75G>T		intron	N/A	ENSP00000359225.4
	CNN3	ENST00000885995.1		c.385-75G>T		intron	N/A	ENSP00000556054.1
	CNN3	ENST00000939684.1		c.379-75G>T		intron	N/A	ENSP00000609743.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000110 AC: 1 AN: 912892 Hom.: 0 Cov.: 12 AF XY: 0.00 AC XY: 0 AN XY: 472418

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 21640

American (AMR) AF: 0.00 AC: 0 AN: 33830

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20640

East Asian (EAS) AF: 0.00 AC: 0 AN: 36466

South Asian (SAS) AF: 0.00 AC: 0 AN: 67972

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49634

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4588

European-Non Finnish (NFE) AF: 0.00000157 AC: 1 AN: 636176

Other (OTH) AF: 0.00 AC: 0 AN: 41946

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.1
DANN	Benign	0.28
PhyloP100		-0.87

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;