rs460879

Variant names:

• chr16-89646481-C-T
• rs460879
• NM_002768.5:c.569+46G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-89646481-C-T
• chr16-89646481-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.705
• Publications: 49 publications found

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]

CHMP1A Gene-Disease associations (from GenCC):

• pontocerebellar hypoplasia type 8

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 1286666.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.507 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002768.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHMP1A	NM_002768.5	MANE Select	c.569+46G>A		intron	N/A	NP_002759.2	Q9HD42-1
	CHMP1A	NM_001083314.4		c.549+46G>A		intron	N/A	NP_001076783.1
	CHMP1A	NR_046418.3		n.857+46G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHMP1A	ENST00000397901.8	TSL:1 MANE Select	c.569+46G>A		intron	N/A	ENSP00000380998.3	Q9HD42-1
	CHMP1A	ENST00000547687.2	TSL:1	n.1317+46G>A		intron	N/A
	CHMP1A	ENST00000675536.1		c.624+46G>A		intron	N/A	ENSP00000501759.1	A0A6Q8PFF8

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

GnomAD2 exomes AF: 0.407 AC: 56819 AN: 139668 AF XY: 0.407

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 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

African (AFR) AF: 0.293 AC: 9062 AN: 30948

American (AMR) AF: 0.308 AC: 10730 AN: 34790

Ashkenazi Jewish (ASJ) AF: 0.565 AC: 13130 AN: 23250

East Asian (EAS) AF: 0.500 AC: 17671 AN: 35314

South Asian (SAS) AF: 0.283 AC: 21166 AN: 74682

European-Finnish (FIN) AF: 0.417 AC: 19754 AN: 47418

Middle Eastern (MID) AF: 0.583 AC: 2568 AN: 4408

European-Non Finnish (NFE) AF: 0.440 AC: 460037 AN: 1044376

Other (OTH) AF: 0.458 AC: 25700 AN: 56058

GnomAD4 genome AF: 0.407 AC: 61944 AN: 152038 Hom.: 13265 Cov.: 33 AF XY: 0.403 AC XY: 29929 AN XY: 74304

African (AFR) AF: 0.294 AC: 12190 AN: 41486

American (AMR) AF: 0.398 AC: 6077 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.558 AC: 1938 AN: 3472

East Asian (EAS) AF: 0.524 AC: 2695 AN: 5144

South Asian (SAS) AF: 0.266 AC: 1283 AN: 4824

European-Finnish (FIN) AF: 0.429 AC: 4545 AN: 10590

Middle Eastern (MID) AF: 0.643 AC: 189 AN: 294

European-Non Finnish (NFE) AF: 0.463 AC: 31465 AN: 67930

Other (OTH) AF: 0.478 AC: 1009 AN: 2112

Alfa AF: 0.448 Hom.: 60593

Bravo AF: 0.406

Asia WGS AF: 0.372 AC: 1293 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.37
DANN	Benign	0.73
PhyloP100		-0.70
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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