Variant 16-89645972-G-A 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_001083314.4(CHMP1A):c.665C>T(p.Ala222Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0194 in 1,611,170 control chromosomes in the GnomAD database, including 5,583 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/5 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.024 ( 662 hom., cov: 33)

Exomes 𝑓: 0.019 ( 4921 hom. )

Consequence

CHMP1A
NM_001083314.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0400

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:

CHMP1A (HGNC:):

CHMP1A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 16-89645972-G-A is Benign according to our data. Variant chr16-89645972-G-A is described in ClinVar as [Benign]. Clinvar id is 380948.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-89645972-G-A is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHMP1A	NM_002768.5 linkuse as main transcript	c.*94C>T		3_prime_UTR_variant	7/7	ENST00000397901.8	NP_002759.2	Q9HD42-1
CHMP1A	NM_001083314.4 linkuse as main transcript	c.665C>T	p.Ala222Val	missense_variant	6/6		NP_001076783.1
CHMP1A	XM_047434195.1 linkuse as main transcript	c.*94C>T		3_prime_UTR_variant	7/7		XP_047290151.1
CHMP1A	NR_046418.3 linkuse as main transcript	n.973C>T		non_coding_transcript_exon_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHMP1A	ENST00000397901.8 linkuse as main transcript	c.*94C>T		3_prime_UTR_variant	7/7	1	NM_002768.5	ENSP00000380998.3		Q9HD42-1

Frequencies

GnomAD3 genomes

AF:

0.0240

AC:

3655

AN:

152160

Hom.:

659

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00359

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00674

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.497

Gnomad SAS

AF:

0.0306

Gnomad FIN

AF:

0.0348

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00398

Gnomad OTH

AF:

0.0220

GnomAD3 exomes

AF:

0.0444

AC:

10783

AN:

243084

Hom.:

2264

AF XY:

0.0417

AC XY:

5540

AN XY:

132764

show subpopulations

Gnomad AFR exome

AF:

0.00389

Gnomad AMR exome

AF:

0.00264

Gnomad ASJ exome

AF:

0.00407

Gnomad EAS exome

AF:

0.508

Gnomad SAS exome

AF:

0.0169

Gnomad FIN exome

AF:

0.0309

Gnomad NFE exome

AF:

0.00377

Gnomad OTH exome

AF:

0.0237

GnomAD4 exome

AF:

0.0190

AC:

27646

AN:

1458892

Hom.:

4921

Cov.:

AF XY:

0.0190

AC XY:

13768

AN XY:

725714

show subpopulations

Gnomad4 AFR exome

AF:

0.00203

Gnomad4 AMR exome

AF:

0.00236

Gnomad4 ASJ exome

AF:

0.00442

Gnomad4 EAS exome

AF:

0.481

Gnomad4 SAS exome

AF:

0.0193

Gnomad4 FIN exome

AF:

0.0291

Gnomad4 NFE exome

AF:

0.00263

Gnomad4 OTH exome

AF:

0.0362

GnomAD4 genome

AF:

0.0240

AC:

3658

AN:

152278

Hom.:

662

Cov.:

AF XY:

0.0271

AC XY:

2019

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.00358

Gnomad4 AMR

AF:

0.00673

Gnomad4 ASJ

AF:

0.00461

Gnomad4 EAS

AF:

0.498

Gnomad4 SAS

AF:

0.0309

Gnomad4 FIN

AF:

0.0348

Gnomad4 NFE

AF:

0.00398

Gnomad4 OTH

AF:

0.0227

Alfa

AF:

0.0203

Hom.:

625

Bravo

AF:

0.0243

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 11, 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. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

7.9

DANN

Benign

0.75

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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