rs35549391

Variant names:

• chr16-83670814-G-A
• rs35549391
• NM_001257.5:c.1126G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-83670814-G-A
• chr16-83670814-G-T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001257.5(CDH13):​c.1126G>A​(p.Ala376Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0069 in 1,613,924 control chromosomes in the GnomAD database, including 45 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0051 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0071 (44 hom.)
• Consequence: CDH13 NM_001257.5 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 3.42
• Publications: 8 publications found

Genes affected

CDH13 (HGNC:1753): (cadherin 13) This gene encodes a member of the cadherin superfamily. The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety, rather than by a transmembrane domain. The protein lacks the cytoplasmic domain characteristic of other cadherins, and so is not thought to be a cell-cell adhesion glycoprotein. This protein acts as a negative regulator of axon growth during neural differentiation. It also protects vascular endothelial cells from apoptosis due to oxidative stress, and is associated with resistance to atherosclerosis. The gene is hypermethylated in many types of cancer. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, May 2011]

LOC124900603 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007640034).
• BP6: Variant 16-83670814-G-A is Benign according to our data. Variant chr16-83670814-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 257642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome4 at 44 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001257.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH13	NM_001257.5	MANE Select	c.1126G>A	p.Ala376Thr	missense	Exon 9 of 14	NP_001248.1	P55290-1
	CDH13	NM_001220488.2		c.1267G>A	p.Ala423Thr	missense	Exon 10 of 15	NP_001207417.1	P55290-4
	CDH13	NM_001220489.2		c.1009G>A	p.Ala337Thr	missense	Exon 8 of 13	NP_001207418.1	P55290-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH13	ENST00000567109.6	TSL:1 MANE Select	c.1126G>A	p.Ala376Thr	missense	Exon 9 of 14	ENSP00000479395.1	P55290-1
	CDH13	ENST00000268613.14	TSL:2	c.1267G>A	p.Ala423Thr	missense	Exon 10 of 15	ENSP00000268613.10	P55290-4
	CDH13	ENST00000428848.7	TSL:2	c.1009G>A	p.Ala337Thr	missense	Exon 8 of 13	ENSP00000394557.3	P55290-5

Frequencies

GnomAD3 genomes AF: 0.00506 AC: 770 AN: 152210 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00145

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00183

Gnomad ASJ AF: 0.0237

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.00141

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00836

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00563 AC: 1404 AN: 249164 AF XY: 0.00581

Gnomad AFR exome AF: 0.000710

Gnomad AMR exome AF: 0.00194

Gnomad ASJ exome AF: 0.0197

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00237

Gnomad NFE exome AF: 0.00843

Gnomad OTH exome AF: 0.00727

GnomAD4 exome AF: 0.00709 AC: 10360 AN: 1461596 Hom.: 44 Cov.: 31 AF XY: 0.00707 AC XY: 5140 AN XY: 727090

African (AFR) AF: 0.00114 AC: 38 AN: 33474

American (AMR) AF: 0.00197 AC: 88 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0191 AC: 500 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00262 AC: 226 AN: 86254

European-Finnish (FIN) AF: 0.00258 AC: 138 AN: 53402

Middle Eastern (MID) AF: 0.00121 AC: 7 AN: 5768

European-Non Finnish (NFE) AF: 0.00805 AC: 8950 AN: 1111780

Other (OTH) AF: 0.00684 AC: 413 AN: 60372

GnomAD4 genome AF: 0.00505 AC: 770 AN: 152328 Hom.: 1 Cov.: 32 AF XY: 0.00452 AC XY: 337 AN XY: 74494

African (AFR) AF: 0.00144 AC: 60 AN: 41566

American (AMR) AF: 0.00183 AC: 28 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0237 AC: 82 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00186 AC: 9 AN: 4826

European-Finnish (FIN) AF: 0.00141 AC: 15 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00836 AC: 569 AN: 68038

Other (OTH) AF: 0.00284 AC: 6 AN: 2112

Alfa AF: 0.00770 Hom.: 10

Bravo AF: 0.00498

TwinsUK AF: 0.00809 AC: 30

ALSPAC AF: 0.00675 AC: 26

ESP6500AA AF: 0.00154 AC: 6

ESP6500EA AF: 0.00700 AC: 58

ExAC AF: 0.00592 AC: 715

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.00862

EpiControl AF: 0.00777

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.067	T
Eigen	Benign	-0.051
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.0076	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.47	N
PhyloP100		3.4
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.14	N
REVEL	Benign	0.093
Sift	Benign	0.18	T
Sift4G	Benign	0.14	T
Polyphen		0.27	B
Vest4		0.18
MVP		0.80
MPC		0.075
ClinPred		0.017	T
GERP RS		5.9
Varity_R		0.12
gMVP		0.44
Mutation Taster		=96/4	polymorphism

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: rs35549391; hg19: chr16-83704419; COSMIC: COSV99075384;