rs36074608

Variant names:

• chr8-99832530-T-C
• rs36074608
• NM_017890.5:c.9567T>C

Your query was ambiguous. Multiple possible variants found:

• chr8-99832530-T-C
• chr8-99832530-T-G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_152564.5(VPS13B):​c.9492T>C​(p.Ser3164Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 1,613,574 control chromosomes in the GnomAD database, including 28,588 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. S3164S) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.16 (2527 hom., cov: 30)
  • Exomes 𝑓: 0.18 (26061 hom.)
• Consequence: VPS13B NM_152564.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:17
• Conservation: PhyloP100: -0.00200
• Publications: 18 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]

VPS13B Gene-Disease associations (from GenCC):

• Cohen syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Myriad Women’s Health, Laboratory for Molecular Medicine, Orphanet, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 8-99832530-T-C is Benign according to our data. Variant chr8-99832530-T-C is described in ClinVar as Benign. ClinVar VariationId is 95875.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.002 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.329 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152564.5. 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.9567T>C	p.Ser3189Ser	synonymous	Exon 52 of 62	NP_060360.3
	VPS13B	NM_152564.5	MANE Select	c.9492T>C	p.Ser3164Ser	synonymous	Exon 52 of 62	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.9567T>C	p.Ser3189Ser	synonymous	Exon 52 of 62	ENSP00000351346.2	Q7Z7G8-1
	VPS13B	ENST00000357162.7	TSL:1 MANE Select	c.9492T>C	p.Ser3164Ser	synonymous	Exon 52 of 62	ENSP00000349685.2	Q7Z7G8-2
	VPS13B	ENST00000682153.1		n.9567T>C		non_coding_transcript_exon	Exon 52 of 62	ENSP00000507923.1	A0A804HKG9

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24757 AN: 151738 Hom.: 2524 Cov.: 30

Gnomad AFR AF: 0.0747

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.312

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.342

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.180

GnomAD2 exomes AF: 0.205 AC: 51563 AN: 251080 AF XY: 0.197

Gnomad AFR exome AF: 0.0742

Gnomad AMR exome AF: 0.400

Gnomad ASJ exome AF: 0.136

Gnomad EAS exome AF: 0.353

Gnomad FIN exome AF: 0.171

Gnomad NFE exome AF: 0.168

Gnomad OTH exome AF: 0.186

GnomAD4 exome AF: 0.180 AC: 263438 AN: 1461720 Hom.: 26061 Cov.: 38 AF XY: 0.179 AC XY: 130222 AN XY: 727138

African (AFR) AF: 0.0703 AC: 2355 AN: 33476

American (AMR) AF: 0.388 AC: 17363 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 3439 AN: 26136

East Asian (EAS) AF: 0.328 AC: 13012 AN: 39694

South Asian (SAS) AF: 0.155 AC: 13358 AN: 86242

European-Finnish (FIN) AF: 0.168 AC: 8988 AN: 53408

Middle Eastern (MID) AF: 0.157 AC: 894 AN: 5694

European-Non Finnish (NFE) AF: 0.174 AC: 193628 AN: 1111972

Other (OTH) AF: 0.172 AC: 10401 AN: 60384

GnomAD4 genome AF: 0.163 AC: 24768 AN: 151854 Hom.: 2527 Cov.: 30 AF XY: 0.168 AC XY: 12497 AN XY: 74198

African (AFR) AF: 0.0749 AC: 3102 AN: 41442

American (AMR) AF: 0.312 AC: 4754 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 435 AN: 3466

East Asian (EAS) AF: 0.342 AC: 1757 AN: 5134

South Asian (SAS) AF: 0.163 AC: 782 AN: 4804

European-Finnish (FIN) AF: 0.170 AC: 1787 AN: 10536

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.170 AC: 11580 AN: 67924

Other (OTH) AF: 0.178 AC: 374 AN: 2104

Alfa AF: 0.162 Hom.: 1406

Bravo AF: 0.173

Asia WGS AF: 0.242 AC: 841 AN: 3478

EpiCase AF: 0.174

EpiControl AF: 0.173

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	8	Cohen syndrome (8)
-	-	6	not specified (6)
-	-	2	not provided (2)
-	-	1	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.6
DANN	Benign	0.59
PhyloP100		-0.0020
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: rs36074608; hg19: chr8-100844758; COSMIC: COSV62149342;