rs6131030

Variant names:

• chr20-46179347-G-A
• rs6131030
• NM_021248.3:c.1664-1150C>T

Your query was ambiguous. Multiple possible variants found:

• chr20-46179347-G-A
• chr20-46179347-G-C

Variant summary

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

The NM_021248.3(CDH22):​c.1664-1150C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 151,998 control chromosomes in the GnomAD database, including 13,432 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 0.42 (13432 hom., cov: 32)
• Consequence: CDH22 NM_021248.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.122
• Publications: 13 publications found

Genes affected

CDH22 (HGNC:13251): (cadherin 22) This gene is a member of the cadherin superfamily. The gene product is composed of five cadherin repeat domains and a cytoplasmic tail similar to the highly conserved cytoplasmic region of classical cadherins. Expressed predominantly in the brain, this putative calcium-dependent cell adhesion protein may play an important role in morphogenesis and tissue formation in neural and non-neural cells during development and maintenance of the brain and neuroendocrine organs. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH22	NM_021248.3	c.1664-1150C>T		intron_variant	Intron 10 of 11	ENST00000537909.4	NP_067071.1
CDH22	XM_011528994.3	c.1664-1150C>T		intron_variant	Intron 10 of 11		XP_011527296.1
CDH22	XM_047440373.1	c.1424-1150C>T		intron_variant	Intron 8 of 9		XP_047296329.1
CDH22	XM_024451966.2	c.1301-1150C>T		intron_variant	Intron 10 of 11		XP_024307734.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH22	ENST00000537909.4	c.1664-1150C>T		intron_variant	Intron 10 of 11	2	NM_021248.3	ENSP00000437790.1

Frequencies

GnomAD3 genomes AF: 0.419 AC: 63581 AN: 151880 Hom.: 13431 Cov.: 32

Gnomad AFR AF: 0.456

Gnomad AMI AF: 0.413

Gnomad AMR AF: 0.453

Gnomad ASJ AF: 0.499

Gnomad EAS AF: 0.536

Gnomad SAS AF: 0.426

Gnomad FIN AF: 0.321

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.389

Gnomad OTH AF: 0.447

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.418 AC: 63600 AN: 151998 Hom.: 13432 Cov.: 32 AF XY: 0.416 AC XY: 30888 AN XY: 74280

African (AFR) AF: 0.455 AC: 18883 AN: 41458

American (AMR) AF: 0.453 AC: 6926 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.499 AC: 1731 AN: 3470

East Asian (EAS) AF: 0.534 AC: 2762 AN: 5170

South Asian (SAS) AF: 0.427 AC: 2056 AN: 4816

European-Finnish (FIN) AF: 0.321 AC: 3393 AN: 10568

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.389 AC: 26409 AN: 67928

Other (OTH) AF: 0.442 AC: 929 AN: 2102

Alfa AF: 0.403 Hom.: 12560

Bravo AF: 0.433

Asia WGS AF: 0.508 AC: 1765 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.6
DANN	Benign	0.76
PhyloP100		0.12
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: rs6131030; hg19: chr20-44807986;