16-89645630-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_002768.5(CHMP1A):c.*436T>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 0.0153 in 312,538 control chromosomes in the GnomAD database, including 72 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.017 (35 hom., cov: 33)
  • Exomes 𝑓: 0.013 (37 hom.)
• Consequence: CHMP1A NM_002768.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.93

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 16-89645630-A-C is Benign according to our data. Variant chr16-89645630-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 1193078.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0173 (2633/152258) while in subpopulation AFR AF= 0.0414 (1721/41544). AF 95% confidence interval is 0.0398. There are 35 homozygotes in gnomad4. There are 1248 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 35 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHMP1A	NM_002768.5	c.*436T>G		3_prime_UTR_variant	7/7	ENST00000397901.8
CHMP1A	NM_001083314.4	c.*284T>G		3_prime_UTR_variant	6/6
CHMP1A	XM_047434195.1	c.*436T>G		3_prime_UTR_variant	7/7
CHMP1A	NR_046418.3	n.1315T>G		non_coding_transcript_exon_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHMP1A	ENST00000397901.8	c.*436T>G		3_prime_UTR_variant	7/7	1	NM_002768.5	P1

Frequencies

GnomAD3 genomes AF: 0.0173 AC: 2632 AN: 152138 Hom.: 35 Cov.: 33

Gnomad AFR AF: 0.0415

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00635

Gnomad ASJ AF: 0.0153

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0387

Gnomad FIN AF: 0.00113

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00793

Gnomad OTH AF: 0.00958

GnomAD4 exome AF: 0.0134 AC: 2149 AN: 160280 Hom.: 37 Cov.: 0 AF XY: 0.0166 AC XY: 1456 AN XY: 87646

Gnomad4 AFR exome AF: 0.0336

Gnomad4 AMR exome AF: 0.00592

Gnomad4 ASJ exome AF: 0.0121

Gnomad4 EAS exome AF: 0.000373

Gnomad4 SAS exome AF: 0.0343

Gnomad4 FIN exome AF: 0.00123

Gnomad4 NFE exome AF: 0.00735

Gnomad4 OTH exome AF: 0.00923

GnomAD4 genome AF: 0.0173 AC: 2633 AN: 152258 Hom.: 35 Cov.: 33 AF XY: 0.0168 AC XY: 1248 AN XY: 74452

Gnomad4 AFR AF: 0.0414

Gnomad4 AMR AF: 0.00634

Gnomad4 ASJ AF: 0.0153

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0385

Gnomad4 FIN AF: 0.00113

Gnomad4 NFE AF: 0.00793

Gnomad4 OTH AF: 0.00995

Alfa AF: 0.00556 Hom.: 2

Bravo AF: 0.0174

Asia WGS AF: 0.0250 AC: 85 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 16, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	0.81
Dann	Benign	0.51
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Other links and lift over

dbSNP: rs78208987; hg19: chr16-89712038;