16-89646325-C-T

Position:

• chr16-89646325-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_002768.5(CHMP1A):​c.569+202G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00737 in 152,336 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency: Genomes: 𝑓 0.0074 (7 hom., cov: 33)
• Consequence: CHMP1A NM_002768.5 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.98

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 16-89646325-C-T is Benign according to our data. Variant chr16-89646325-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1189878.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00737 (1123/152336) while in subpopulation NFE AF= 0.0129 (879/68026). AF 95% confidence interval is 0.0122. There are 7 homozygotes in gnomad4. There are 520 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	Protein	UniProt
CHMP1A	NM_002768.5	c.569+202G>A		intron_variant		ENST00000397901.8	NP_002759.2
CHMP1A	NM_001083314.4	c.549+202G>A		intron_variant			NP_001076783.1
CHMP1A	XM_047434195.1	c.377+202G>A		intron_variant			XP_047290151.1
CHMP1A	NR_046418.3	n.857+202G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHMP1A	ENST00000397901.8	c.569+202G>A		intron_variant		1	NM_002768.5	ENSP00000380998	P1

Frequencies

GnomAD3 genomes AF: 0.00737 AC: 1122 AN: 152218 Hom.: 7 Cov.: 33

Gnomad AFR AF: 0.00181

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.00255

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00904

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0129

Gnomad OTH AF: 0.00478

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00737 AC: 1123 AN: 152336 Hom.: 7 Cov.: 33 AF XY: 0.00698 AC XY: 520 AN XY: 74492

Gnomad4 AFR AF: 0.00185

Gnomad4 AMR AF: 0.00255

Gnomad4 ASJ AF: 0.000577

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.00904

Gnomad4 NFE AF: 0.0129

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.00821 Hom.: 0

Bravo AF: 0.00625

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 17, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.23
DANN	Benign	0.75

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: rs62068734; hg19: chr16-89712733;