16-89646481-C-T

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.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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.705

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 16-89646481-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_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHMP1A	NM_002768.5	c.569+46G>A		intron_variant		ENST00000397901.8
CHMP1A	NM_001083314.4	c.549+46G>A		intron_variant
CHMP1A	XM_047434195.1	c.377+46G>A		intron_variant
CHMP1A	NR_046418.3	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	c.569+46G>A		intron_variant		1	NM_002768.5	P1

Frequencies

GnomAD3 genomes AF: 0.408 AC: 61921 AN: 151922 Hom.: 13255 Cov.: 33

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

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.: 26 AF XY: 0.426 AC XY: 282009 AN XY: 662014

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.: 33 AF XY: 0.403 AC XY: 29929 AN XY: 74304

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

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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

Other links and lift over

dbSNP: rs460879; hg19: chr16-89712889; COSMIC: COSV53683926; COSMIC: COSV53683926;