2-96819077-C-T

Position:

• chr2-96819077-C-T

Variant summary

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

The ENST00000305510.4(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 ENST00000305510.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNNM3	NM_017623.5	c.1225+1575C>T		intron_variant		ENST00000305510.4	NP_060093.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNNM3	ENST00000305510.4	c.1225+1575C>T		intron_variant		1	NM_017623.5	ENSP00000305449	P1
CNNM3	ENST00000377060.7	c.1225+1575C>T		intron_variant		2		ENSP00000366260

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

Gnomad4 AFR AF: 0.0622

Gnomad4 AMR AF: 0.369

Gnomad4 ASJ AF: 0.308

Gnomad4 EAS AF: 0.544

Gnomad4 SAS AF: 0.666

Gnomad4 FIN AF: 0.176

Gnomad4 NFE AF: 0.222

Gnomad4 OTH AF: 0.250

Alfa AF: 0.236 Hom.: 4241

Bravo AF: 0.222

Asia WGS AF: 0.552 AC: 1915 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.88
DANN	Benign	0.47

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: rs4907251; hg19: chr2-97484814;