Genetic Variant NM_020348.3:c.2176+3603C>A (chr10-99368605-C-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.410

Publications

1 publications found

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CNNM1	NM_020348.3	MANE Select	c.2176+3603C>A	intron	N/A	NP_065081.2	Q9NRU3-1
CNNM1	NM_001345887.2		c.2177-13C>A	intron	N/A	NP_001332816.1	A0A8Q3SIV9
CNNM1	NM_001345889.2		c.2177-13C>A	intron	N/A	NP_001332818.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CNNM1	ENST00000356713.5	TSL:1 MANE Select	c.2176+3603C>A	intron	N/A	ENSP00000349147.4	Q9NRU3-1
CNNM1	ENST00000696687.1		c.2177-13C>A	intron	N/A	ENSP00000512809.1	A0A8Q3SIV9
CNNM1	ENST00000914274.1		c.2176+3603C>A	intron	N/A	ENSP00000584333.1

Frequencies

GnomAD3 genomes

AF:

0.0544

AC:

8266

AN:

151950

Hom.:

312

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.0511

AC:

6881

AN:

134544

AF XY:

0.0530

show subpopulations

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 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.:

AF XY:

0.0719

AC XY:

40075

AN XY:

557440

show subpopulations

African (AFR)

AF:

0.00910

AC:

222

AN:

24398

American (AMR)

AF:

0.0237

AC:

670

AN:

28264

Ashkenazi Jewish (ASJ)

AF:

0.0398

AC:

635

AN:

15942

East Asian (EAS)

AF:

0.0000779

AC:

AN:

12840

South Asian (SAS)

AF:

0.0437

AC:

3331

AN:

76192

European-Finnish (FIN)

AF:

0.0980

AC:

1281

AN:

13078

Middle Eastern (MID)

AF:

0.0338

AC:

149

AN:

4402

European-Non Finnish (NFE)

AF:

0.0806

AC:

74140

AN:

919508

Other (OTH)

AF:

0.0601

AC:

2495

AN:

41498

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.449

Heterozygous variant carriers

3387

6774

10161

13548

16935

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3096

6192

9288

12384

15480

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0544

AC:

8266

AN:

152068

Hom.:

312

Cov.:

AF XY:

0.0547

AC XY:

4063

AN XY:

74302

show subpopulations

African (AFR)

AF:

0.0135

AC:

559

AN:

41494

American (AMR)

AF:

0.0396

AC:

605

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.0450

AC:

156

AN:

3468

East Asian (EAS)

AF:

0.000386

AC:

AN:

5182

South Asian (SAS)

AF:

0.0442

AC:

212

AN:

4798

European-Finnish (FIN)

AF:

0.0941

AC:

993

AN:

10558

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0809

AC:

5499

AN:

67980

Other (OTH)

AF:

0.0389

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

392

785

1177

1570

1962

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

204

306

408

510

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0667

Hom.:

686

Bravo

AF:

0.0478

Asia WGS

AF:

0.00982

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Benign

0.76

PhyloP100

0.41

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over