rs1261256

Variant names:

• chr5-22454987-T-C
• rs1261256
• NM_004061.5:c.-427-49636A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.09
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CDH12	NM_004061.5	c.-427-49636A>G		intron_variant	Intron 2 of 14	ENST00000382254.6	NP_004052.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH12	ENST00000382254.6	c.-427-49636A>G		intron_variant	Intron 2 of 14	1	NM_004061.5	ENSP00000371689.1
CDH12	ENST00000504376.6	c.-333+50283A>G		intron_variant	Intron 2 of 13	5		ENSP00000423577.1
CDH12	ENST00000520668.1	n.393-49636A>G		intron_variant	Intron 2 of 3	4

Frequencies

GnomAD3 genomes AF: 0.472 AC: 71741 AN: 151942 Hom.: 17341 Cov.: 32

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

African (AFR) AF: 0.438 AC: 18174 AN: 41476

American (AMR) AF: 0.644 AC: 9842 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.546 AC: 1894 AN: 3468

East Asian (EAS) AF: 0.461 AC: 2378 AN: 5160

South Asian (SAS) AF: 0.381 AC: 1837 AN: 4820

European-Finnish (FIN) AF: 0.396 AC: 4184 AN: 10556

Middle Eastern (MID) AF: 0.551 AC: 162 AN: 294

European-Non Finnish (NFE) AF: 0.467 AC: 31722 AN: 67992

Other (OTH) AF: 0.516 AC: 1089 AN: 2112

Alfa AF: 0.468 Hom.: 8872

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
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1261256; hg19: chr5-22455096;