Variant 16-89646481-C-T 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.569+46G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 1,503,282 control chromosomes in the GnomAD database, including 140,236 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.41 ( 13265 hom., cov: 33)

Exomes 𝑓: 0.43 ( 126971 hom. )

Consequence

CHMP1A
NM_002768.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.705

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=-0.83).

BP6

Variant 16-89646481-C-T is Benign according to our data. Variant chr16-89646481-C-T is described in ClinVar as [Benign]. Clinvar id is 1286666.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
CHMP1A	NM_002768.5 linkuse as main transcript	c.569+46G>A	intron_variant	ENST00000397901.8
CHMP1A	NM_001083314.4 linkuse as main transcript	c.549+46G>A	intron_variant
CHMP1A	XM_047434195.1 linkuse as main transcript	c.377+46G>A	intron_variant
CHMP1A	NR_046418.3 linkuse as main transcript	n.857+46G>A	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHMP1A	ENST00000397901.8 linkuse as main transcript	c.569+46G>A		intron_variant		1	NM_002768.5	P1	Q9HD42-1

Frequencies

GnomAD3 genomes

AF:

0.408

AC:

61921

AN:

151922

Hom.:

13255

Cov.:

show subpopulations

Gnomad AFR

AF:

0.294

Gnomad AMI

AF:

0.608

Gnomad AMR

AF:

0.398

Gnomad ASJ

AF:

0.558

Gnomad EAS

AF:

0.523

Gnomad SAS

AF:

0.264

Gnomad FIN

AF:

0.429

Gnomad MID

AF:

0.642

Gnomad NFE

AF:

0.463

Gnomad OTH

AF:

0.482

GnomAD3 exomes

AF:

0.407

AC:

56819

AN:

139668

Hom.:

12321

AF XY:

0.407

AC XY:

29821

AN XY:

73192

show subpopulations

Gnomad AFR exome

AF:

0.291

Gnomad AMR exome

AF:

0.297

Gnomad ASJ exome

AF:

0.568

Gnomad EAS exome

AF:

0.530

Gnomad SAS exome

AF:

0.281

Gnomad FIN exome

AF:

0.409

Gnomad NFE exome

AF:

0.466

Gnomad OTH exome

AF:

0.486

GnomAD4 exome

AF:

0.429

AC:

579818

AN:

1351244

Hom.:

126971

Cov.:

AF XY:

0.426

AC XY:

282009

AN XY:

662014

show subpopulations

Gnomad4 AFR exome

AF:

0.293

Gnomad4 AMR exome

AF:

0.308

Gnomad4 ASJ exome

AF:

0.565

Gnomad4 EAS exome

AF:

0.500

Gnomad4 SAS exome

AF:

0.283

Gnomad4 FIN exome

AF:

0.417

Gnomad4 NFE exome

AF:

0.440

Gnomad4 OTH exome

AF:

0.458

GnomAD4 genome

AF:

0.407

AC:

61944

AN:

152038

Hom.:

13265

Cov.:

AF XY:

0.403

AC XY:

29929

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.294

Gnomad4 AMR

AF:

0.398

Gnomad4 ASJ

AF:

0.558

Gnomad4 EAS

AF:

0.524

Gnomad4 SAS

AF:

0.266

Gnomad4 FIN

AF:

0.429

Gnomad4 NFE

AF:

0.463

Gnomad4 OTH

AF:

0.478

Alfa

AF:

0.463

Hom.:

27504

Bravo

AF:

0.406

Asia WGS

AF:

0.372

AC:

1293

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 26, 2018	- -
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

-0.83

CADD

Benign

0.37

DANN

Benign

0.73

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