dbSNP rs862991: 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:

Genome browser will be placed here

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
CADM3	NM_001127173.3 link	c.691+534G>A	intron_variant	Intron 5 of 8	ENST00000368125.9	NP_001120645.1
CADM3	NM_021189.5 link	c.793+534G>A	intron_variant	Intron 6 of 9		NP_067012.1
CADM3	NM_001346510.2 link	c.553+672G>A	intron_variant	Intron 5 of 8		NP_001333439.1
CADM3	XM_024448760.2 link	c.940+534G>A	intron_variant	Intron 8 of 11		XP_024304528.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CADM3	ENST00000368125.9 link	c.691+534G>A		intron_variant	Intron 5 of 8	1	NM_001127173.3	ENSP00000357107.4

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over