chr16-83779909-A-G

Variant names:

• chr16-83779909-A-G
• rs16961737
• NM_001257.5:c.1682-59A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001257.5(CDH13):​c.1682-59A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 1,107,094 control chromosomes in the GnomAD database, including 32,527 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3938 hom., cov: 32)
  • Exomes 𝑓: 0.22 (28589 hom.)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.735
• Publications: 5 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]

HSBP1 (HGNC:5203): (heat shock factor binding protein 1) The heat-shock response is elicited by exposure of cells to thermal and chemical stress and through the activation of HSFs (heat shock factors) results in the elevated expression of heat-shock induced genes. Heat shock factor binding protein 1 (HSBP1), is a 76-amino-acid protein that binds to heat shock factor 1(HSF1), which is a transcription factor involved in the HS response. During HS response, HSF1 undergoes conformational transition from an inert non-DNA-binding monomer to active functional trimers. HSBP1 is nuclear-localized and interacts with the active trimeric state of HSF1 to negatively regulate HSF1 DNA-binding activity. Overexpression of HSBP1 in mammalian cells represses the transactivation activity of HSF1. When overexpressed in C.elegans HSBP1 has severe effects on survival of the animals after thermal and chemical stress consistent with a role of HSBP1 as a negative regulator of heat shock response. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 16-83779909-A-G is Benign according to our data. Variant chr16-83779909-A-G is described in ClinVar as Benign. ClinVar VariationId is 1278402.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.595 is higher than 0.05.

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.1682-59A>G		intron	N/A	NP_001248.1	P55290-1
	CDH13	NM_001220488.2		c.1823-59A>G		intron	N/A	NP_001207417.1	P55290-4
	CDH13	NM_001220489.2		c.1565-59A>G		intron	N/A	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.1682-59A>G		intron	N/A	ENSP00000479395.1	P55290-1
	CDH13	ENST00000268613.14	TSL:2	c.1823-59A>G		intron	N/A	ENSP00000268613.10	P55290-4
	CDH13	ENST00000428848.7	TSL:2	c.1565-59A>G		intron	N/A	ENSP00000394557.3	P55290-5

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30481 AN: 151894 Hom.: 3939 Cov.: 32

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.613

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.220

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.231

GnomAD4 exome AF: 0.219 AC: 208921 AN: 955082 Hom.: 28589 AF XY: 0.221 AC XY: 107167 AN XY: 484026

African (AFR) AF: 0.104 AC: 2356 AN: 22578

American (AMR) AF: 0.413 AC: 12804 AN: 30996

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 4558 AN: 19332

East Asian (EAS) AF: 0.654 AC: 23565 AN: 36042

South Asian (SAS) AF: 0.319 AC: 20507 AN: 64340

European-Finnish (FIN) AF: 0.223 AC: 11158 AN: 50012

Middle Eastern (MID) AF: 0.288 AC: 1334 AN: 4624

European-Non Finnish (NFE) AF: 0.180 AC: 122834 AN: 684206

Other (OTH) AF: 0.228 AC: 9805 AN: 42952

GnomAD4 genome AF: 0.201 AC: 30492 AN: 152012 Hom.: 3938 Cov.: 32 AF XY: 0.210 AC XY: 15582 AN XY: 74286

African (AFR) AF: 0.103 AC: 4289 AN: 41516

American (AMR) AF: 0.335 AC: 5117 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 827 AN: 3468

East Asian (EAS) AF: 0.613 AC: 3136 AN: 5116

South Asian (SAS) AF: 0.338 AC: 1630 AN: 4818

European-Finnish (FIN) AF: 0.230 AC: 2429 AN: 10562

Middle Eastern (MID) AF: 0.226 AC: 66 AN: 292

European-Non Finnish (NFE) AF: 0.182 AC: 12380 AN: 67954

Other (OTH) AF: 0.231 AC: 488 AN: 2112

Alfa AF: 0.0979 Hom.: 156

Bravo AF: 0.206

Asia WGS AF: 0.446 AC: 1550 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.23
DANN	Benign	0.33
PhyloP100		-0.73
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: rs16961737; hg19: chr16-83813514; COSMIC: COSV51844177;