NM_017890.5:c.11821-296T>C

Variant names:

• chr8-99875122-T-C
• rs10955222
• NM_017890.5:c.11821-296T>C

Variant summary

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

The NM_017890.5(VPS13B):​c.11821-296T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 419,322 control chromosomes in the GnomAD database, including 3,730 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1297 hom., cov: 32)
  • Exomes 𝑓: 0.13 (2433 hom.)
• Consequence: VPS13B NM_017890.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.854
• Publications: 4 publications found

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]

COX6C (HGNC:2285): (cytochrome c oxidase subunit 6C) Cytochrome c oxidase, the terminal enzyme of the mitochondrial respiratory chain, catalyzes the electron transfer from reduced cytochrome c to oxygen. It is a heteromeric complex consisting of 3 catalytic subunits encoded by mitochondrial genes and multiple structural subunits encoded by nuclear genes. The mitochondrially-encoded subunits function in electron transfer, and the nuclear-encoded subunits may be involved in the regulation and assembly of the complex. This nuclear gene encodes subunit VIc, which has 77% amino acid sequence identity with mouse subunit VIc. This gene is up-regulated in prostate cancer cells. A pseudogene has been found on chromosomes 16p12. [provided by RefSeq, Jul 2010]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 8-99875122-T-C is Benign according to our data. Variant chr8-99875122-T-C is described in ClinVar as Benign. ClinVar VariationId is 1266835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017890.5. 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
	VPS13B	NM_017890.5	MANE Plus Clinical	c.11821-296T>C		intron	N/A	NP_060360.3
	VPS13B	NM_152564.5	MANE Select	c.11746-296T>C		intron	N/A	NP_689777.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VPS13B	ENST00000358544.7	TSL:1 MANE Plus Clinical	c.11821-296T>C		intron	N/A	ENSP00000351346.2	Q7Z7G8-1
	VPS13B	ENST00000357162.7	TSL:1 MANE Select	c.11746-296T>C		intron	N/A	ENSP00000349685.2	Q7Z7G8-2
	VPS13B	ENST00000493587.1	TSL:2	n.1323-296T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19475 AN: 152098 Hom.: 1299 Cov.: 32

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.0932

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.125

GnomAD4 exome AF: 0.128 AC: 34217 AN: 267106 Hom.: 2433 Cov.: 2 AF XY: 0.127 AC XY: 18102 AN XY: 142578

African (AFR) AF: 0.113 AC: 928 AN: 8184

American (AMR) AF: 0.137 AC: 1585 AN: 11572

Ashkenazi Jewish (ASJ) AF: 0.203 AC: 1573 AN: 7740

East Asian (EAS) AF: 0.103 AC: 1498 AN: 14558

South Asian (SAS) AF: 0.103 AC: 3813 AN: 37098

European-Finnish (FIN) AF: 0.103 AC: 1355 AN: 13096

Middle Eastern (MID) AF: 0.144 AC: 162 AN: 1122

European-Non Finnish (NFE) AF: 0.134 AC: 21224 AN: 158734

Other (OTH) AF: 0.139 AC: 2079 AN: 15002

GnomAD4 genome AF: 0.128 AC: 19478 AN: 152216 Hom.: 1297 Cov.: 32 AF XY: 0.126 AC XY: 9396 AN XY: 74416

African (AFR) AF: 0.111 AC: 4602 AN: 41542

American (AMR) AF: 0.122 AC: 1872 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 708 AN: 3466

East Asian (EAS) AF: 0.116 AC: 602 AN: 5190

South Asian (SAS) AF: 0.0935 AC: 451 AN: 4822

European-Finnish (FIN) AF: 0.118 AC: 1249 AN: 10596

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.139 AC: 9468 AN: 68004

Other (OTH) AF: 0.124 AC: 261 AN: 2106

Alfa AF: 0.134 Hom.: 607

Bravo AF: 0.132

Asia WGS AF: 0.116 AC: 404 AN: 3478

ClinVar

ClinVar submissions

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	-0.81
CADD	Benign	0.37
DANN	Benign	0.67
PhyloP100		-0.85
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs10955222; hg19: chr8-100887350;