10-99361030-C-T

Position:

• chr10-99361030-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_020348.3(CNNM1):​c.1858+55C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 1,515,510 control chromosomes in the GnomAD database, including 264,029 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.47 (19858 hom., cov: 32)
  • Exomes 𝑓: 0.59 (244171 hom.)
• Consequence: CNNM1 NM_020348.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.374

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 10-99361030-C-T is Benign according to our data. Variant chr10-99361030-C-T is described in ClinVar as [Benign]. Clinvar id is 1268829.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNNM1	NM_020348.3	c.1858+55C>T		intron_variant		ENST00000356713.5	NP_065081.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNNM1	ENST00000356713.5	c.1858+55C>T		intron_variant		1	NM_020348.3	ENSP00000349147.4
CNNM1	ENST00000696687.1	c.1858+55C>T		intron_variant				ENSP00000512809.1

Frequencies

GnomAD3 genomes AF: 0.472 AC: 71740 AN: 151918 Hom.: 19850 Cov.: 32

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.754

Gnomad AMR AF: 0.511

Gnomad ASJ AF: 0.566

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.555

Gnomad FIN AF: 0.587

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.617

Gnomad OTH AF: 0.527

GnomAD4 exome AF: 0.593 AC: 808422 AN: 1363474 Hom.: 244171 AF XY: 0.593 AC XY: 396758 AN XY: 668874

Gnomad4 AFR exome AF: 0.144

Gnomad4 AMR exome AF: 0.514

Gnomad4 ASJ exome AF: 0.563

Gnomad4 EAS exome AF: 0.494

Gnomad4 SAS exome AF: 0.557

Gnomad4 FIN exome AF: 0.593

Gnomad4 NFE exome AF: 0.617

Gnomad4 OTH exome AF: 0.568

GnomAD4 genome AF: 0.472 AC: 71769 AN: 152036 Hom.: 19858 Cov.: 32 AF XY: 0.474 AC XY: 35238 AN XY: 74328

Gnomad4 AFR AF: 0.164

Gnomad4 AMR AF: 0.512

Gnomad4 ASJ AF: 0.566

Gnomad4 EAS AF: 0.469

Gnomad4 SAS AF: 0.555

Gnomad4 FIN AF: 0.587

Gnomad4 NFE AF: 0.617

Gnomad4 OTH AF: 0.526

Alfa AF: 0.404 Hom.: 1275

Bravo AF: 0.453

Asia WGS AF: 0.465 AC: 1617 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 10, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.3
DANN	Benign	0.60

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: rs3763792; hg19: chr10-101120787; COSMIC: COSV63200295;