Variant 16-89645674-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_002768.5(CHMP1A):c.*392C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0063 in 349,006 control chromosomes in the GnomAD database, including 47 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 41 hom., cov: 33)

Exomes 𝑓: 0.0011 ( 6 hom. )

Consequence

CHMP1A
NM_002768.5 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.471

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:

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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=-0.91).

BP6

Variant 16-89645674-G-C is Benign according to our data. Variant chr16-89645674-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1207156.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.013 (1976/152260) while in subpopulation AFR AF= 0.0452 (1876/41530). AF 95% confidence interval is 0.0435. There are 41 homozygotes in gnomad4. There are 899 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 41 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
CHMP1A	NM_002768.5 linkuse as main transcript	c.*392C>G	3_prime_UTR_variant	7/7	ENST00000397901.8	NP_002759.2
CHMP1A	NM_001083314.4 linkuse as main transcript	c.*240C>G	3_prime_UTR_variant	6/6		NP_001076783.1
CHMP1A	XM_047434195.1 linkuse as main transcript	c.*392C>G	3_prime_UTR_variant	7/7		XP_047290151.1
CHMP1A	NR_046418.3 linkuse as main transcript	n.1271C>G	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.*392C>G		3_prime_UTR_variant	7/7	1	NM_002768.5	ENSP00000380998	P1	Q9HD42-1

Frequencies

GnomAD3 genomes

AF:

0.0130

AC:

1972

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0452

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00425

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:

0.0119

GnomAD4 exome

AF:

0.00112

AC:

221

AN:

196746

Hom.:

Cov.:

AF XY:

0.000852

AC XY:

AN XY:

106806

show subpopulations

Gnomad4 AFR exome

AF:

0.0411

Gnomad4 AMR exome

AF:

0.00258

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000601

Gnomad4 OTH exome

AF:

0.00200

GnomAD4 genome

AF:

0.0130

AC:

1976

AN:

152260

Hom.:

Cov.:

AF XY:

0.0121

AC XY:

899

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.0452

Gnomad4 AMR

AF:

0.00425

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:

0.0118

Alfa

AF:

0.000423

Hom.:

Bravo

AF:

0.0151

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 26, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.69

DANN

Benign

0.23

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