Genetic Variant CADM3:c.691+534G>A (chr1-159194574-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001127173.3(CADM3):c.691+534G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.671 in 152,340 control chromosomes in the GnomAD database, including 35,254 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 0.67 ( 35216 hom., cov: 33)

Exomes 𝑓: 0.66 ( 38 hom. )

Consequence

CADM3
NM_001127173.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.488

Publications

7 publications found

Variant links:

Genes affected

CADM3 (HGNC:17601): (cell adhesion molecule 3) The protein encoded by this gene is a calcium-independent cell-cell adhesion protein that can form homodimers or heterodimers with other nectin proteins. The encoded protein has both homophilic and heterophilic cell-cell adhesion activity. This gene is reported to be a tumor suppressor gene. [provided by RefSeq, Oct 2016]

CADM3 links:

CADM3-AS1 (HGNC:40812): (CADM3 antisense RNA 1)

CADM3-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.905 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001127173.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CADM3	NM_001127173.3	MANE Select	c.691+534G>A	intron	N/A	NP_001120645.1
CADM3	NM_021189.5		c.793+534G>A	intron	N/A	NP_067012.1
CADM3	NM_001346510.2		c.553+672G>A	intron	N/A	NP_001333439.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CADM3	ENST00000368125.9	TSL:1 MANE Select	c.691+534G>A	intron	N/A	ENSP00000357107.4
CADM3	ENST00000368124.8	TSL:1	c.793+534G>A	intron	N/A	ENSP00000357106.4
CADM3	ENST00000416746.1	TSL:1	c.553+672G>A	intron	N/A	ENSP00000387802.1

Frequencies

GnomAD3 genomes

AF:

0.672

AC:

102124

AN:

152046

Hom.:

35207

Cov.:

show subpopulations

Gnomad AFR

AF:

0.523

Gnomad AMI

AF:

0.841

Gnomad AMR

AF:

0.680

Gnomad ASJ

AF:

0.711

Gnomad EAS

AF:

0.927

Gnomad SAS

AF:

0.745

Gnomad FIN

AF:

0.738

Gnomad MID

AF:

0.630

Gnomad NFE

AF:

0.720

Gnomad OTH

AF:

0.692

GnomAD4 exome

AF:

0.665

AC:

117

AN:

176

Hom.:

Cov.:

AF XY:

0.688

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AF:

0.667

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

1.00

AC:

AN:

European-Finnish (FIN)

AF:

0.583

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.662

AC:

AN:

142

Other (OTH)

AF:

0.625

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.537

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.671

AC:

102164

AN:

152164

Hom.:

35216

Cov.:

AF XY:

0.672

AC XY:

50014

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.523

AC:

21673

AN:

41474

American (AMR)

AF:

0.681

AC:

10407

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.711

AC:

2470

AN:

3472

East Asian (EAS)

AF:

0.927

AC:

4812

AN:

5190

South Asian (SAS)

AF:

0.745

AC:

3590

AN:

4820

European-Finnish (FIN)

AF:

0.738

AC:

7822

AN:

10598

Middle Eastern (MID)

AF:

0.636

AC:

187

AN:

294

European-Non Finnish (NFE)

AF:

0.720

AC:

48966

AN:

67998

Other (OTH)

AF:

0.695

AC:

1470

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1659

3319

4978

6638

8297

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

812

1624

2436

3248

4060

<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:

0.706

Hom.:

109032

Bravo

AF:

0.665

Asia WGS

AF:

0.796

AC:

2767

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.17

(source)

DANN

Benign

0.39

PhyloP100

-0.49

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over