Menu
GeneBe

11-115229156-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001301043.2(CADM1):c.678G>A(p.Ala226=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00141 in 1,614,014 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0077 ( 20 hom., cov: 33)
Exomes 𝑓: 0.00075 ( 15 hom. )

Consequence

CADM1
NM_001301043.2 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -5.37
Variant links:
Genes affected
CADM1 (HGNC:5951): (cell adhesion molecule 1) Enables signaling receptor binding activity. Involved in several processes, including cell recognition; positive regulation of cytokine production; and susceptibility to natural killer cell mediated cytotoxicity. Located in plasma membrane. Implicated in breast carcinoma and prostate cancer. Biomarker of cervix uteri carcinoma in situ. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.6).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 11-115229156-C-T is Benign according to our data. Variant chr11-115229156-C-T is described in ClinVar as [Benign]. Clinvar id is 779315.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-5.37 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00772 (1176/152302) while in subpopulation AFR AF= 0.0268 (1113/41554). AF 95% confidence interval is 0.0255. There are 20 homozygotes in gnomad4. There are 536 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 1177 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CADM1NM_001301043.2 linkuse as main transcriptc.678G>A p.Ala226= synonymous_variant 5/12 ENST00000331581.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CADM1ENST00000331581.11 linkuse as main transcriptc.678G>A p.Ala226= synonymous_variant 5/121 NM_001301043.2 P4Q9BY67-3

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00773
AC:
1177
AN:
152184
Hom.:
20
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0269
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00236
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.000147
Gnomad OTH
AF:
0.00669
GnomAD3 exomes
AF:
0.00206
AC:
517
AN:
250820
Hom.:
5
AF XY:
0.00145
AC XY:
196
AN XY:
135568
show subpopulations
Gnomad AFR exome
AF:
0.0289
Gnomad AMR exome
AF:
0.00110
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000618
Gnomad OTH exome
AF:
0.000327
GnomAD4 exome
AF:
0.000749
AC:
1095
AN:
1461712
Hom.:
15
Cov.:
31
AF XY:
0.000666
AC XY:
484
AN XY:
727162
show subpopulations
Gnomad4 AFR exome
AF:
0.0265
Gnomad4 AMR exome
AF:
0.00145
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000459
Gnomad4 OTH exome
AF:
0.00136
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00772
AC:
1176
AN:
152302
Hom.:
20
Cov.:
33
AF XY:
0.00720
AC XY:
536
AN XY:
74472
show subpopulations
Gnomad4 AFR
AF:
0.0268
Gnomad4 AMR
AF:
0.00235
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000147
Gnomad4 OTH
AF:
0.00662
Alfa
AF:
0.00361
Hom.:
3
Bravo
AF:
0.00890
Asia WGS
AF:
0.00144
AC:
5
AN:
3478
EpiCase
AF:
0.000164
EpiControl
AF:
0.000119

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.60
Cadd
Benign
7.6
Dann
Benign
0.65
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs138595924; hg19: chr11-115099876; COSMIC: COSV59004519; COSMIC: COSV59004519; API