dbSNP rs17568778: CNNM1: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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNNM1	NM_020348.3 link	c.2176+3603C>A		intron_variant	Intron 6 of 10	ENST00000356713.5	NP_065081.2	Q9NRU3-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CNNM1	ENST00000356713.5 link	c.2176+3603C>A	intron_variant	Intron 6 of 10	1	NM_020348.3	ENSP00000349147.4	Q9NRU3-1
CNNM1	ENST00000488090.1 link	n.269C>A	non_coding_transcript_exon_variant	Exon 1 of 2	2
CNNM1	ENST00000696687.1 link	c.2177-13C>A	intron_variant	Intron 6 of 11			ENSP00000512809.1	A0A8Q3SIV9

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 v4.3

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over