10-99361030-C-T

Variant names:

• chr10-99361030-C-T
• rs3763792
• NM_020348.3:c.1858+55C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020348.3. 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
	CNNM1	NM_020348.3	MANE Select	c.1858+55C>T		intron	N/A	NP_065081.2	Q9NRU3-1
	CNNM1	NM_001345887.2		c.1858+55C>T		intron	N/A	NP_001332816.1	A0A8Q3SIV9
	CNNM1	NM_001345889.2		c.1858+55C>T		intron	N/A	NP_001332818.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNNM1	ENST00000356713.5	TSL:1 MANE Select	c.1858+55C>T		intron	N/A	ENSP00000349147.4	Q9NRU3-1
	CNNM1	ENST00000696687.1		c.1858+55C>T		intron	N/A	ENSP00000512809.1	A0A8Q3SIV9
	CNNM1	ENST00000914274.1		c.1858+55C>T		intron	N/A	ENSP00000584333.1

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

African (AFR) AF: 0.144 AC: 4445 AN: 30800

American (AMR) AF: 0.514 AC: 16998 AN: 33056

Ashkenazi Jewish (ASJ) AF: 0.563 AC: 12358 AN: 21932

East Asian (EAS) AF: 0.494 AC: 18663 AN: 37762

South Asian (SAS) AF: 0.557 AC: 41647 AN: 74706

European-Finnish (FIN) AF: 0.593 AC: 28752 AN: 48460

Middle Eastern (MID) AF: 0.553 AC: 2977 AN: 5386

European-Non Finnish (NFE) AF: 0.617 AC: 650566 AN: 1055006

Other (OTH) AF: 0.568 AC: 32016 AN: 56366

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

African (AFR) AF: 0.164 AC: 6822 AN: 41492

American (AMR) AF: 0.512 AC: 7817 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.566 AC: 1960 AN: 3464

East Asian (EAS) AF: 0.469 AC: 2424 AN: 5166

South Asian (SAS) AF: 0.555 AC: 2671 AN: 4810

European-Finnish (FIN) AF: 0.587 AC: 6198 AN: 10552

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.617 AC: 41937 AN: 67970

Other (OTH) AF: 0.526 AC: 1111 AN: 2112

Alfa AF: 0.497 Hom.: 5094

Bravo AF: 0.453

Asia WGS AF: 0.465 AC: 1617 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.3
DANN	Benign	0.60
PhyloP100		0.37
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: rs3763792; hg19: chr10-101120787; COSMIC: COSV63200295;