Variant 16-89645730-T-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.*336A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0243 in 493,614 control chromosomes in the GnomAD database, including 2,046 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.024 ( 681 hom., cov: 33)

Exomes 𝑓: 0.024 ( 1365 hom. )

Consequence

CHMP1A
NM_002768.5 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.16

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 16-89645730-T-G is Benign according to our data. Variant chr16-89645730-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 1223455.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.486 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
CHMP1A	NM_002768.5 linkuse as main transcript	c.*336A>C	3_prime_UTR_variant	7/7	ENST00000397901.8	NP_002759.2
CHMP1A	NM_001083314.4 linkuse as main transcript	c.*184A>C	3_prime_UTR_variant	6/6		NP_001076783.1
CHMP1A	XM_047434195.1 linkuse as main transcript	c.*336A>C	3_prime_UTR_variant	7/7		XP_047290151.1
CHMP1A	NR_046418.3 linkuse as main transcript	n.1215A>C	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.*336A>C		3_prime_UTR_variant	7/7	1	NM_002768.5	ENSP00000380998	P1	Q9HD42-1

Frequencies

GnomAD3 genomes

AF:

0.0243

AC:

3691

AN:

152158

Hom.:

678

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00674

Gnomad ASJ

AF:

0.00462

Gnomad EAS

AF:

0.501

Gnomad SAS

AF:

0.0302

Gnomad FIN

AF:

0.0348

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00398

Gnomad OTH

AF:

0.0220

GnomAD4 exome

AF:

0.0243

AC:

8280

AN:

341338

Hom.:

1365

Cov.:

AF XY:

0.0239

AC XY:

4284

AN XY:

178980

show subpopulations

Gnomad4 AFR exome

AF:

0.00230

Gnomad4 AMR exome

AF:

0.00226

Gnomad4 ASJ exome

AF:

0.00454

Gnomad4 EAS exome

AF:

0.445

Gnomad4 SAS exome

AF:

0.0200

Gnomad4 FIN exome

AF:

0.0248

Gnomad4 NFE exome

AF:

0.00286

Gnomad4 OTH exome

AF:

0.0265

GnomAD4 genome

AF:

0.0243

AC:

3694

AN:

152276

Hom.:

681

Cov.:

AF XY:

0.0274

AC XY:

2043

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.00361

Gnomad4 AMR

AF:

0.00673

Gnomad4 ASJ

AF:

0.00462

Gnomad4 EAS

AF:

0.502

Gnomad4 SAS

AF:

0.0305

Gnomad4 FIN

AF:

0.0348

Gnomad4 NFE

AF:

0.00398

Gnomad4 OTH

AF:

0.0227

Alfa

AF:

0.0113

Hom.:

Bravo

AF:

0.0244

Asia WGS

AF:

0.217

AC:

752

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 28, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.70

DANN

Benign

0.21

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