rs994430

Variant names:

• chr2-96773264-A-T
• rs994430
• NM_020184.4:c.1402+10863A>T

Variant summary

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

The NM_020184.4(CNNM4):​c.1402+10863A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 152,128 control chromosomes in the GnomAD database, including 17,080 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 0.45 (17080 hom., cov: 33)
• Consequence: CNNM4 NM_020184.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.111
• Publications: 8 publications found

Genes affected

CNNM4 (HGNC:105): (cyclin and CBS domain divalent metal cation transport mediator 4) This gene encodes a member of the ancient conserved domain containing protein family. Members of this protein family contain a cyclin box motif and have structural similarity to the cyclins. The encoded protein may play a role in metal ion transport. Mutations in this gene are associated with Jalili syndrome which consists of cone-rod dystrophy and amelogenesis imperfecta. [provided by RefSeq, Feb 2010]

CNNM4 Gene-Disease associations (from GenCC):

• Jalili syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, Orphanet, ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.639 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNNM4	NM_020184.4	c.1402+10863A>T		intron_variant	Intron 1 of 6	ENST00000377075.3	NP_064569.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNNM4	ENST00000377075.3	c.1402+10863A>T		intron_variant	Intron 1 of 6	1	NM_020184.4	ENSP00000366275.2

Frequencies

GnomAD3 genomes AF: 0.454 AC: 69087 AN: 152010 Hom.: 17049 Cov.: 33

Gnomad AFR AF: 0.645

Gnomad AMI AF: 0.332

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.388

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.487

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.401

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

GnomAD4 genome AF: 0.455 AC: 69165 AN: 152128 Hom.: 17080 Cov.: 33 AF XY: 0.451 AC XY: 33552 AN XY: 74368

African (AFR) AF: 0.645 AC: 26793 AN: 41516

American (AMR) AF: 0.325 AC: 4972 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.323 AC: 1119 AN: 3468

East Asian (EAS) AF: 0.387 AC: 2002 AN: 5176

South Asian (SAS) AF: 0.229 AC: 1106 AN: 4824

European-Finnish (FIN) AF: 0.487 AC: 5142 AN: 10566

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.394 AC: 26765 AN: 67984

Other (OTH) AF: 0.400 AC: 844 AN: 2108

Alfa AF: 0.428 Hom.: 2050

Bravo AF: 0.454

Asia WGS AF: 0.349 AC: 1216 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.1
DANN	Benign	0.84
PhyloP100		0.11
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: rs994430; hg19: chr2-97439001;