rs3751692

Variant names:

• chr16-89645730-T-G
• rs3751692
• NM_002768.5:c.*336A>C

Your query was ambiguous. Multiple possible variants found:

• chr16-89645730-T-G
• chr16-89645730-T-A

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.*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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.16
• Publications: 2 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 16-89645730-T-G is Benign according to our data. Variant chr16-89645730-T-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1223455.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.486 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.*336A>C		3_prime_UTR	Exon 7 of 7	NP_002759.2	Q9HD42-1
	CHMP1A	NM_001083314.4		c.*184A>C		3_prime_UTR	Exon 6 of 6	NP_001076783.1
	CHMP1A	NR_046418.3		n.1215A>C		non_coding_transcript_exon	Exon 7 of 7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHMP1A	ENST00000397901.8	TSL:1 MANE Select	c.*336A>C		3_prime_UTR	Exon 7 of 7	ENSP00000380998.3	Q9HD42-1
	CHMP1A	ENST00000547687.2	TSL:1	n.1675A>C		non_coding_transcript_exon	Exon 2 of 2
	CHMP1A	ENST00000675536.1		c.*184A>C		3_prime_UTR	Exon 7 of 7	ENSP00000501759.1	A0A6Q8PFF8

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

African (AFR) AF: 0.00230 AC: 20 AN: 8686

American (AMR) AF: 0.00226 AC: 26 AN: 11506

Ashkenazi Jewish (ASJ) AF: 0.00454 AC: 39 AN: 8590

East Asian (EAS) AF: 0.445 AC: 5831 AN: 13090

South Asian (SAS) AF: 0.0200 AC: 884 AN: 44294

European-Finnish (FIN) AF: 0.0248 AC: 369 AN: 14868

Middle Eastern (MID) AF: 0.00857 AC: 11 AN: 1284

European-Non Finnish (NFE) AF: 0.00286 AC: 633 AN: 221410

Other (OTH) AF: 0.0265 AC: 467 AN: 17610

GnomAD4 genome AF: 0.0243 AC: 3694 AN: 152276 Hom.: 681 Cov.: 33 AF XY: 0.0274 AC XY: 2043 AN XY: 74458

African (AFR) AF: 0.00361 AC: 150 AN: 41570

American (AMR) AF: 0.00673 AC: 103 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00462 AC: 16 AN: 3466

East Asian (EAS) AF: 0.502 AC: 2590 AN: 5162

South Asian (SAS) AF: 0.0305 AC: 147 AN: 4826

European-Finnish (FIN) AF: 0.0348 AC: 369 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00398 AC: 271 AN: 68008

Other (OTH) AF: 0.0227 AC: 48 AN: 2116

Alfa AF: 0.0113 Hom.: 13

Bravo AF: 0.0244

Asia WGS AF: 0.217 AC: 752 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely 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	0.70
DANN	Benign	0.21
PhyloP100		-1.2
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: rs3751692; hg19: chr16-89712138; COSMIC: COSV53682395; COSMIC: COSV53682395;