rs4907251

Variant names:

• chr2-96819077-C-T
• rs4907251
• NM_017623.5:c.1225+1575C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017623.5(CNNM3):​c.1225+1575C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 152,050 control chromosomes in the GnomAD database, including 5,242 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 0.22 (5242 hom., cov: 32)
• Consequence: CNNM3 NM_017623.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05
• Publications: 14 publications found

Genes affected

CNNM3 (HGNC:104): (cyclin and CBS domain divalent metal cation transport mediator 3) Predicted to enable transmembrane transporter activity. Predicted to be involved in ion transport; magnesium ion homeostasis; and transmembrane transport. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

CNNM3-DT (HGNC:53592): (CNNM3 divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017623.5. 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
	CNNM3	NM_017623.5	MANE Select	c.1225+1575C>T		intron	N/A	NP_060093.3
	CNNM3	NM_199078.3		c.1225+1575C>T		intron	N/A	NP_951060.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNNM3	ENST00000305510.4	TSL:1 MANE Select	c.1225+1575C>T		intron	N/A	ENSP00000305449.3
	CNNM3	ENST00000947263.1		c.1225+1575C>T		intron	N/A	ENSP00000617322.1
	CNNM3	ENST00000947265.1		c.1225+1575C>T		intron	N/A	ENSP00000617324.1

Frequencies

GnomAD3 genomes AF: 0.217 AC: 33008 AN: 151932 Hom.: 5225 Cov.: 32

Gnomad AFR AF: 0.0624

Gnomad AMI AF: 0.217

Gnomad AMR AF: 0.368

Gnomad ASJ AF: 0.308

Gnomad EAS AF: 0.543

Gnomad SAS AF: 0.665

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.245

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

GnomAD4 genome AF: 0.217 AC: 33038 AN: 152050 Hom.: 5242 Cov.: 32 AF XY: 0.226 AC XY: 16832 AN XY: 74314

African (AFR) AF: 0.0622 AC: 2582 AN: 41484

American (AMR) AF: 0.369 AC: 5643 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.308 AC: 1070 AN: 3470

East Asian (EAS) AF: 0.544 AC: 2813 AN: 5168

South Asian (SAS) AF: 0.666 AC: 3210 AN: 4822

European-Finnish (FIN) AF: 0.176 AC: 1863 AN: 10572

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.222 AC: 15064 AN: 67942

Other (OTH) AF: 0.250 AC: 526 AN: 2108

Alfa AF: 0.232 Hom.: 5916

Bravo AF: 0.222

Asia WGS AF: 0.552 AC: 1915 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.88
DANN	Benign	0.47
PhyloP100		-1.1
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: rs4907251; hg19: chr2-97484814;