rs118061300

chr8-99819365-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_017890.5(VPS13B):c.8697-47C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00739 in 1,600,524 control chromosomes in the GnomAD database, including 60 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0056 (6 hom., cov: 32)
  • Exomes 𝑓: 0.0076 (54 hom.)
• Consequence: VPS13B NM_017890.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.634

Genes affected

VPS13B (HGNC:2183): (vacuolar protein sorting 13 homolog B) This gene encodes a potential transmembrane protein that may function in vesicle-mediated transport and sorting of proteins within the cell. This protein may play a role in the development and the function of the eye, hematological system, and central nervous system. Mutations in this gene have been associated with Cohen syndrome. Multiple splice variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 8-99819365-C-T is Benign according to our data. Variant chr8-99819365-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 262665.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-99819365-C-T is described in Lovd as [Benign].
• BS2: High Homozygotes in GnomAd at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VPS13B	NM_017890.5	c.8697-47C>T		intron_variant		ENST00000358544.7
VPS13B	NM_152564.5	c.8622-47C>T		intron_variant		ENST00000357162.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VPS13B	ENST00000357162.7	c.8622-47C>T		intron_variant		1	NM_152564.5	P1
VPS13B	ENST00000358544.7	c.8697-47C>T		intron_variant		1	NM_017890.5

Frequencies

GnomAD3 genomes AF: 0.00557 AC: 848 AN: 152128 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.00113

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.00138

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.0112

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00916

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00497 AC: 1230 AN: 247482 Hom.: 5 AF XY: 0.00483 AC XY: 649 AN XY: 134454

Gnomad AFR exome AF: 0.00118

Gnomad AMR exome AF: 0.00145

Gnomad ASJ exome AF: 0.00309

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000788

Gnomad FIN exome AF: 0.00827

Gnomad NFE exome AF: 0.00809

Gnomad OTH exome AF: 0.00417

GnomAD4 exome AF: 0.00758 AC: 10983 AN: 1448278 Hom.: 54 Cov.: 29 AF XY: 0.00739 AC XY: 5329 AN XY: 721432

Gnomad4 AFR exome AF: 0.000786

Gnomad4 AMR exome AF: 0.00130

Gnomad4 ASJ exome AF: 0.00338

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000629

Gnomad4 FIN exome AF: 0.00929

Gnomad4 NFE exome AF: 0.00903

Gnomad4 OTH exome AF: 0.00546

GnomAD4 genome AF: 0.00557 AC: 848 AN: 152246 Hom.: 6 Cov.: 32 AF XY: 0.00528 AC XY: 393 AN XY: 74458

Gnomad4 AFR AF: 0.00113

Gnomad4 AMR AF: 0.00137

Gnomad4 ASJ AF: 0.00403

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.0112

Gnomad4 NFE AF: 0.00916

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00724 Hom.: 2

Bravo AF: 0.00465

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
Cadd	Benign	10
Dann	Benign	0.67

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

Other links and lift over

dbSNP: rs118061300; hg19: chr8-100831593;