16-89646215-A-C

Position:

• chr16-89646215-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.570-128T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00158 in 862,720 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0060 (7 hom., cov: 33)
  • Exomes 𝑓: 0.00063 (5 hom.)
• Consequence: CHMP1A NM_002768.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.984

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=-0.84).
• BP6: Variant 16-89646215-A-C is Benign according to our data. Variant chr16-89646215-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 1207637.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00601 (915/152286) while in subpopulation AFR AF= 0.021 (873/41556). AF 95% confidence interval is 0.0199. There are 7 homozygotes in gnomad4. There are 448 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHMP1A	NM_002768.5	c.570-128T>G		intron_variant		ENST00000397901.8
CHMP1A	NM_001083314.4	c.550-128T>G		intron_variant
CHMP1A	XM_047434195.1	c.378-128T>G		intron_variant
CHMP1A	NR_046418.3	n.858-128T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHMP1A	ENST00000397901.8	c.570-128T>G		intron_variant		1	NM_002768.5	P1

Frequencies

GnomAD3 genomes AF: 0.00602 AC: 916 AN: 152168 Hom.: 7 Cov.: 33

Gnomad AFR AF: 0.0211

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00216

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00239

GnomAD4 exome AF: 0.000635 AC: 451 AN: 710434 Hom.: 5 AF XY: 0.000576 AC XY: 208 AN XY: 361168

Gnomad4 AFR exome AF: 0.0203

Gnomad4 AMR exome AF: 0.00147

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000192

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000481

Gnomad4 OTH exome AF: 0.00128

GnomAD4 genome AF: 0.00601 AC: 915 AN: 152286 Hom.: 7 Cov.: 33 AF XY: 0.00602 AC XY: 448 AN XY: 74476

Gnomad4 AFR AF: 0.0210

Gnomad4 AMR AF: 0.00216

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00236

Alfa AF: 0.00517 Hom.: 2

Bravo AF: 0.00695

Asia WGS AF: 0.000289 AC: 1 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

Sep 18, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.61
DANN	Benign	0.53

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: rs141857967; hg19: chr16-89712623;