Variant 16-89646107-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002768.5(CHMP1A):c.570-20G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00287 in 1,537,428 control chromosomes in the GnomAD database, including 122 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 58 hom., cov: 33)

Exomes 𝑓: 0.0016 ( 64 hom. )

Consequence

CHMP1A
NM_002768.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.684

Variant links:

Genes affected

CHMP1A (HGNC:8740): (charged multivesicular body protein 1A) This gene encodes a member of the CHMP/Chmp family of proteins which are involved in multivesicular body sorting of proteins to the interiors of lysosomes. The initial prediction of the protein sequence encoded by this gene suggested that the encoded protein was a metallopeptidase. The nomenclature has been updated recently to reflect the correct biological function of this encoded protein. Several transcripts encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2012]

CHMP1A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 16-89646107-C-G is Benign according to our data. Variant chr16-89646107-C-G is described in ClinVar as [Benign]. Clinvar id is 384619.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0541 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
CHMP1A	NM_002768.5 linkuse as main transcript	c.570-20G>C	intron_variant	ENST00000397901.8	NP_002759.2
CHMP1A	NM_001083314.4 linkuse as main transcript	c.550-20G>C	intron_variant		NP_001076783.1
CHMP1A	XM_047434195.1 linkuse as main transcript	c.378-20G>C	intron_variant		XP_047290151.1
CHMP1A	NR_046418.3 linkuse as main transcript	n.858-20G>C	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHMP1A	ENST00000397901.8 linkuse as main transcript	c.570-20G>C		intron_variant		1	NM_002768.5	ENSP00000380998	P1	Q9HD42-1

Frequencies

GnomAD3 genomes

AF:

0.0148

AC:

2247

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0513

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00549

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.0129

GnomAD3 exomes

AF:

0.00468

AC:

880

AN:

187856

Hom.:

AF XY:

0.00342

AC XY:

342

AN XY:

100090

show subpopulations

Gnomad AFR exome

AF:

0.0546

Gnomad AMR exome

AF:

0.00285

Gnomad ASJ exome

AF:

0.000428

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000147

Gnomad OTH exome

AF:

0.000917

GnomAD4 exome

AF:

0.00156

AC:

2155

AN:

1385114

Hom.:

Cov.:

AF XY:

0.00134

AC XY:

909

AN XY:

680480

show subpopulations

Gnomad4 AFR exome

AF:

0.0563

Gnomad4 AMR exome

AF:

0.00313

Gnomad4 ASJ exome

AF:

0.000470

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000541

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000633

Gnomad4 OTH exome

AF:

0.00335

GnomAD4 genome

AF:

0.0148

AC:

2255

AN:

152314

Hom.:

Cov.:

AF XY:

0.0139

AC XY:

1032

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.0513

Gnomad4 AMR

AF:

0.00549

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.0128

Alfa

AF:

0.00699

Hom.:

Bravo

AF:

0.0171

Asia WGS

AF:

0.00375

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 26, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 16, 2016

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.98

DANN

Benign

0.30

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over