rs17568778

Positions:

• chr10-99368605-C-A
• chr10-99368605-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_020348.3(CNNM1):​c.2176+3603C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0708 in 1,288,190 control chromosomes in the GnomAD database, including 3,720 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 0.054 (312 hom., cov: 32)
  • Exomes 𝑓: 0.073 (3408 hom.)
• Consequence: CNNM1 NM_020348.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.410

Genes affected

CNNM1 (HGNC:102): (cyclin and CBS domain divalent metal cation transport mediator 1) This gene encodes a member of the ancient conserved domain protein family. The encoded protein may bind copper. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]

CNNM1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0791 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNNM1	NM_020348.3	c.2176+3603C>A		intron_variant		ENST00000356713.5	NP_065081.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNNM1	ENST00000356713.5	c.2176+3603C>A		intron_variant		1	NM_020348.3	ENSP00000349147.4
CNNM1	ENST00000696687.1	c.2177-13C>A		intron_variant				ENSP00000512809.1
CNNM1	ENST00000488090.1	n.269C>A		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes AF: 0.0544 AC: 8266 AN: 151950 Hom.: 312 Cov.: 32

Gnomad AFR AF: 0.0135

Gnomad AMI AF: 0.172

Gnomad AMR AF: 0.0397

Gnomad ASJ AF: 0.0450

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0437

Gnomad FIN AF: 0.0941

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0809

Gnomad OTH AF: 0.0398

GnomAD3 exomes AF: 0.0511 AC: 6881 AN: 134544 Hom.: 274 AF XY: 0.0530 AC XY: 3882 AN XY: 73282

Gnomad AFR exome AF: 0.0132

Gnomad AMR exome AF: 0.0247

Gnomad ASJ exome AF: 0.0418

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0441

Gnomad FIN exome AF: 0.101

Gnomad NFE exome AF: 0.0778

Gnomad OTH exome AF: 0.0490

GnomAD4 exome AF: 0.0730 AC: 82924 AN: 1136122 Hom.: 3408 Cov.: 30 AF XY: 0.0719 AC XY: 40075 AN XY: 557440

Gnomad4 AFR exome AF: 0.00910

Gnomad4 AMR exome AF: 0.0237

Gnomad4 ASJ exome AF: 0.0398

Gnomad4 EAS exome AF: 0.0000779

Gnomad4 SAS exome AF: 0.0437

Gnomad4 FIN exome AF: 0.0980

Gnomad4 NFE exome AF: 0.0806

Gnomad4 OTH exome AF: 0.0601

GnomAD4 genome AF: 0.0544 AC: 8266 AN: 152068 Hom.: 312 Cov.: 32 AF XY: 0.0547 AC XY: 4063 AN XY: 74302

Gnomad4 AFR AF: 0.0135

Gnomad4 AMR AF: 0.0396

Gnomad4 ASJ AF: 0.0450

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0442

Gnomad4 FIN AF: 0.0941

Gnomad4 NFE AF: 0.0809

Gnomad4 OTH AF: 0.0389

Alfa AF: 0.0679 Hom.: 554

Bravo AF: 0.0478

Asia WGS AF: 0.00982 AC: 35 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	19
DANN	Benign	0.76

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: rs17568778; hg19: chr10-101128362;