rs1261256

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004061.5(CDH12):​c.-427-49636A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 152,060 control chromosomes in the GnomAD database, including 17,353 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 0.47 ( 17353 hom., cov: 32)

Consequence

CDH12
NM_004061.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.09
Variant links:
Genes affected
CDH12 (HGNC:1751): (cadherin 12) This gene encodes a type II classical cadherin of the cadherin superfamily. Alternative splicing of this gene results in multiple transcript variants. At least one of these variants encodes a preproprotein that is proteolytically processed to generate the mature cadherin protein. These integral membrane proteins mediate calcium-dependent cell-cell adhesion and are composed of a large N-terminal extracellular domain, a single membrane-spanning domain, and a small, highly conserved C-terminal cytoplasmic domain. Type II (atypical) cadherins are defined based on their lack of a histidine-alanine-valine (HAV) cell adhesion recognition sequence specific to type I cadherins. This particular cadherin appears to be expressed specifically in the brain and its temporal pattern of expression would be consistent with a role during a critical period of neuronal development, perhaps specifically during synaptogenesis. [provided by RefSeq, Nov 2015]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.93).
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.634 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CDH12NM_004061.5 linkuse as main transcriptc.-427-49636A>G intron_variant ENST00000382254.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CDH12ENST00000382254.6 linkuse as main transcriptc.-427-49636A>G intron_variant 1 NM_004061.5 P1P55289-1
CDH12ENST00000504376.6 linkuse as main transcriptc.-333+50283A>G intron_variant 5 P1P55289-1
CDH12ENST00000520668.1 linkuse as main transcriptn.393-49636A>G intron_variant, non_coding_transcript_variant 4

Frequencies

GnomAD3 genomes
AF:
0.472
AC:
71741
AN:
151942
Hom.:
17341
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.438
Gnomad AMI
AF:
0.563
Gnomad AMR
AF:
0.644
Gnomad ASJ
AF:
0.546
Gnomad EAS
AF:
0.462
Gnomad SAS
AF:
0.382
Gnomad FIN
AF:
0.396
Gnomad MID
AF:
0.538
Gnomad NFE
AF:
0.467
Gnomad OTH
AF:
0.515
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.472
AC:
71794
AN:
152060
Hom.:
17353
Cov.:
32
AF XY:
0.471
AC XY:
35005
AN XY:
74306
show subpopulations
Gnomad4 AFR
AF:
0.438
Gnomad4 AMR
AF:
0.644
Gnomad4 ASJ
AF:
0.546
Gnomad4 EAS
AF:
0.461
Gnomad4 SAS
AF:
0.381
Gnomad4 FIN
AF:
0.396
Gnomad4 NFE
AF:
0.467
Gnomad4 OTH
AF:
0.516
Alfa
AF:
0.467
Hom.:
7901
Bravo
AF:
0.499
Asia WGS
AF:
0.416
AC:
1448
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
0.21
DANN
Benign
0.52

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: rs1261256; hg19: chr5-22455096; API