16-89645972-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002768.5(CHMP1A):c.*94C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0194 in 1,611,170 control chromosomes in the GnomAD database, including 5,583 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.024 (662 hom., cov: 33)
  • Exomes 𝑓: 0.019 (4921 hom.)
• Consequence: CHMP1A NM_002768.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0400

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=-0.79).
• BP6: Variant 16-89645972-G-A is Benign according to our data. Variant chr16-89645972-G-A is described in ClinVar as [Benign]. Clinvar id is 380948.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-89645972-G-A is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHMP1A	NM_002768.5	c.*94C>T		3_prime_UTR_variant	7/7	ENST00000397901.8
CHMP1A	NM_001083314.4	c.665C>T	p.Ala222Val	missense_variant	6/6
CHMP1A	XM_047434195.1	c.*94C>T		3_prime_UTR_variant	7/7
CHMP1A	NR_046418.3	n.973C>T		non_coding_transcript_exon_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHMP1A	ENST00000397901.8	c.*94C>T		3_prime_UTR_variant	7/7	1	NM_002768.5	P1

Frequencies

GnomAD3 genomes AF: 0.0240 AC: 3655 AN: 152160 Hom.: 659 Cov.: 33

Gnomad AFR AF: 0.00359

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00674

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.497

Gnomad SAS AF: 0.0306

Gnomad FIN AF: 0.0348

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00398

Gnomad OTH AF: 0.0220

GnomAD3 exomes AF: 0.0444 AC: 10783 AN: 243084 Hom.: 2264 AF XY: 0.0417 AC XY: 5540 AN XY: 132764

Gnomad AFR exome AF: 0.00389

Gnomad AMR exome AF: 0.00264

Gnomad ASJ exome AF: 0.00407

Gnomad EAS exome AF: 0.508

Gnomad SAS exome AF: 0.0169

Gnomad FIN exome AF: 0.0309

Gnomad NFE exome AF: 0.00377

Gnomad OTH exome AF: 0.0237

GnomAD4 exome AF: 0.0190 AC: 27646 AN: 1458892 Hom.: 4921 Cov.: 31 AF XY: 0.0190 AC XY: 13768 AN XY: 725714

Gnomad4 AFR exome AF: 0.00203

Gnomad4 AMR exome AF: 0.00236

Gnomad4 ASJ exome AF: 0.00442

Gnomad4 EAS exome AF: 0.481

Gnomad4 SAS exome AF: 0.0193

Gnomad4 FIN exome AF: 0.0291

Gnomad4 NFE exome AF: 0.00263

Gnomad4 OTH exome AF: 0.0362

GnomAD4 genome AF: 0.0240 AC: 3658 AN: 152278 Hom.: 662 Cov.: 33 AF XY: 0.0271 AC XY: 2019 AN XY: 74444

Gnomad4 AFR AF: 0.00358

Gnomad4 AMR AF: 0.00673

Gnomad4 ASJ AF: 0.00461

Gnomad4 EAS AF: 0.498

Gnomad4 SAS AF: 0.0309

Gnomad4 FIN AF: 0.0348

Gnomad4 NFE AF: 0.00398

Gnomad4 OTH AF: 0.0227

Alfa AF: 0.0203 Hom.: 625

Bravo AF: 0.0243

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 11, 2016

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	7.9
Dann	Benign	0.75
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

Other links and lift over

dbSNP: rs116954456; hg19: chr16-89712380; COSMIC: COSV53683530; COSMIC: COSV53683530;