16-89645730-T-G

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.*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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.16

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=-0.83).
• 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_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.486 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHMP1A	NM_002768.5	c.*336A>C		3_prime_UTR_variant	7/7	ENST00000397901.8
CHMP1A	NM_001083314.4	c.*184A>C		3_prime_UTR_variant	6/6
CHMP1A	XM_047434195.1	c.*336A>C		3_prime_UTR_variant	7/7
CHMP1A	NR_046418.3	n.1215A>C		non_coding_transcript_exon_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHMP1A	ENST00000397901.8	c.*336A>C		3_prime_UTR_variant	7/7	1	NM_002768.5	P1

Frequencies

GnomAD3 genomes AF: 0.0243 AC: 3691 AN: 152158 Hom.: 678 Cov.: 33

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.: 5 AF XY: 0.0239 AC XY: 4284 AN XY: 178980

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.: 33 AF XY: 0.0274 AC XY: 2043 AN XY: 74458

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.: 13

Bravo AF: 0.0244

Asia WGS AF: 0.217 AC: 752 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 28, 2018

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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

Other links and lift over

dbSNP: rs3751692; hg19: chr16-89712138; COSMIC: COSV53682395; COSMIC: COSV53682395;