17-80997348-GC-G

Position:

• chr17-80997348-GC-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_024591.5(CHMP6):​c.495+14delC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0431 in 1,467,210 control chromosomes in the GnomAD database, including 4,689 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.14 (1127 hom., cov: 0)
  • Exomes 𝑓: 0.038 (3562 hom.)
• Consequence: CHMP6 NM_024591.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.92

Genes affected

CHMP6 (HGNC:25675): (charged multivesicular body protein 6) This gene encodes a member of the chromatin-modifying protein/charged multivesicular body protein family. Proteins in this family are part of the ESCRT-III (endosomal sorting complex required for transport III) which degrades surface receptors, and in biosynthesis of endosomes. [provided by RefSeq, Mar 2012]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 17-80997348-GC-G is Benign according to our data. Variant chr17-80997348-GC-G is described in ClinVar as [Benign]. Clinvar id is 775393.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHMP6	NM_024591.5	c.495+14delC		intron_variant		ENST00000325167.9	NP_078867.2
CHMP6	XM_005257668.1	c.495+14delC		intron_variant			XP_005257725.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHMP6	ENST00000325167.9	c.495+14delC		intron_variant		1	NM_024591.5	ENSP00000317468.5
CHMP6	ENST00000572778.5	c.432+14delC		intron_variant		2		ENSP00000461098.1
CHMP6	ENST00000571457.1	c.369+14delC		intron_variant		3		ENSP00000461238.1
CHMP6	ENST00000572525.5	c.237+14delC		intron_variant		3		ENSP00000460389.1

Frequencies

GnomAD3 genomes AF: 0.138 AC: 9923 AN: 71728 Hom.: 1121 Cov.: 0

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0728

Gnomad ASJ AF: 0.0157

Gnomad EAS AF: 0.0130

Gnomad SAS AF: 0.0269

Gnomad FIN AF: 0.00770

Gnomad MID AF: 0.0449

Gnomad NFE AF: 0.00780

Gnomad OTH AF: 0.101

GnomAD3 exomes AF: 0.113 AC: 17087 AN: 150980 Hom.: 1752 AF XY: 0.105 AC XY: 8685 AN XY: 82726

Gnomad AFR exome AF: 0.319

Gnomad AMR exome AF: 0.114

Gnomad ASJ exome AF: 0.0641

Gnomad EAS exome AF: 0.100

Gnomad SAS exome AF: 0.0684

Gnomad FIN exome AF: 0.0623

Gnomad NFE exome AF: 0.105

Gnomad OTH exome AF: 0.0897

GnomAD4 exome AF: 0.0382 AC: 53260 AN: 1395392 Hom.: 3562 Cov.: 30 AF XY: 0.0370 AC XY: 25761 AN XY: 695974

Gnomad4 AFR exome AF: 0.252

Gnomad4 AMR exome AF: 0.0523

Gnomad4 ASJ exome AF: 0.0230

Gnomad4 EAS exome AF: 0.0215

Gnomad4 SAS exome AF: 0.0330

Gnomad4 FIN exome AF: 0.0147

Gnomad4 NFE exome AF: 0.0333

Gnomad4 OTH exome AF: 0.0417

GnomAD4 genome AF: 0.139 AC: 9959 AN: 71818 Hom.: 1127 Cov.: 0 AF XY: 0.132 AC XY: 4686 AN XY: 35490

Gnomad4 AFR AF: 0.295

Gnomad4 AMR AF: 0.0728

Gnomad4 ASJ AF: 0.0157

Gnomad4 EAS AF: 0.0130

Gnomad4 SAS AF: 0.0264

Gnomad4 FIN AF: 0.00770

Gnomad4 NFE AF: 0.00780

Gnomad4 OTH AF: 0.100

Asia WGS AF: 0.0480 AC: 113 AN: 2358

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 19, 2017

- -

Computational scores

Source: dbNSFP v4.3

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: rs11362653; hg19: chr17-78971148;