Variant chr16-89646215-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_002768.5(CHMP1A):c.570-128T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00158 in 862,720 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0060 ( 7 hom., cov: 33)

Exomes 𝑓: 0.00063 ( 5 hom. )

Consequence

CHMP1A
NM_002768.5 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.984

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 16-89646215-A-C is Benign according to our data. Variant chr16-89646215-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 1207637.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00601 (915/152286) while in subpopulation AFR AF= 0.021 (873/41556). AF 95% confidence interval is 0.0199. There are 7 homozygotes in gnomad4. There are 448 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
CHMP1A	NM_002768.5 linkuse as main transcript	c.570-128T>G	intron_variant	ENST00000397901.8	NP_002759.2
CHMP1A	NM_001083314.4 linkuse as main transcript	c.550-128T>G	intron_variant		NP_001076783.1
CHMP1A	XM_047434195.1 linkuse as main transcript	c.378-128T>G	intron_variant		XP_047290151.1
CHMP1A	NR_046418.3 linkuse as main transcript	n.858-128T>G	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.570-128T>G		intron_variant		1	NM_002768.5	ENSP00000380998	P1	Q9HD42-1

Frequencies

GnomAD3 genomes

AF:

0.00602

AC:

916

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0211

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00216

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00239

GnomAD4 exome

AF:

0.000635

AC:

451

AN:

710434

Hom.:

AF XY:

0.000576

AC XY:

208

AN XY:

361168

show subpopulations

Gnomad4 AFR exome

AF:

0.0203

Gnomad4 AMR exome

AF:

0.00147

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000192

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000481

Gnomad4 OTH exome

AF:

0.00128

GnomAD4 genome

AF:

0.00601

AC:

915

AN:

152286

Hom.:

Cov.:

AF XY:

0.00602

AC XY:

448

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.0210

Gnomad4 AMR

AF:

0.00216

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.00517

Hom.:

Bravo

AF:

0.00695

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 18, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.61

DANN

Benign

0.53

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