dbSNP rs117555004: CHMP1A:c.*100T>G (chr16-89645966-A-C) – ACMG Classification: Benign (-18 pts)

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_001083314.4(CHMP1A):c.671T>G(p.Leu224Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0195 in 1,611,186 control chromosomes in the GnomAD database, including 5,600 homozygotes. In-silico tool predicts a benign outcome for this variant. 6/6 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.024 ( 664 hom., cov: 33)

Exomes 𝑓: 0.019 ( 4936 hom. )

Consequence

CHMP1A
NM_001083314.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.531

Publications

6 publications found

Variant links:

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

CHMP1A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -18 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.063).

BP6

Variant 16-89645966-A-C is Benign according to our data. Variant chr16-89645966-A-C is described in ClinVar as Benign. ClinVar VariationId is 380949.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001083314.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CHMP1A	NM_002768.5	MANE Select	c.*100T>G		3_prime_UTR	Exon 7 of 7	NP_002759.2	Q9HD42-1
CHMP1A	NM_001083314.4		c.671T>G	p.Leu224Arg	missense	Exon 6 of 6	NP_001076783.1
CHMP1A	NR_046418.3		n.979T>G		non_coding_transcript_exon	Exon 7 of 7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CHMP1A	ENST00000397901.8	TSL:1 MANE Select	c.*100T>G		3_prime_UTR	Exon 7 of 7	ENSP00000380998.3	Q9HD42-1
CHMP1A	ENST00000547687.2	TSL:1	n.1439T>G		non_coding_transcript_exon	Exon 2 of 2
CHMP1A	ENST00000675536.1		c.746T>G	p.Leu249Arg	missense	Exon 7 of 7	ENSP00000501759.1	A0A6Q8PFF8

Frequencies

GnomAD3 genomes

AF:

0.0240

AC:

3652

AN:

152172

Hom.:

661

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00674

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.497

Gnomad SAS

AF:

0.0306

Gnomad FIN

AF:

0.0348

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00394

Gnomad OTH

AF:

0.0220

GnomAD2 exomes

AF:

0.0443

AC:

10766

AN:

242812

AF XY:

0.0417

show subpopulations

Gnomad AFR exome

AF:

0.00385

Gnomad AMR exome

AF:

0.00267

Gnomad ASJ exome

AF:

0.00417

Gnomad EAS exome

AF:

0.508

Gnomad FIN exome

AF:

0.0307

Gnomad NFE exome

AF:

0.00371

Gnomad OTH exome

AF:

0.0235

GnomAD4 exome

AF:

0.0190

AC:

27697

AN:

1458896

Hom.:

4936

Cov.:

AF XY:

0.0190

AC XY:

13805

AN XY:

725746

show subpopulations

African (AFR)

AF:

0.00203

AC:

AN:

33434

American (AMR)

AF:

0.00238

AC:

106

AN:

44538

Ashkenazi Jewish (ASJ)

AF:

0.00442

AC:

115

AN:

26022

East Asian (EAS)

AF:

0.483

AC:

19064

AN:

39508

South Asian (SAS)

AF:

0.0198

AC:

1701

AN:

85964

European-Finnish (FIN)

AF:

0.0292

AC:

1528

AN:

52382

Middle Eastern (MID)

AF:

0.00652

AC:

AN:

5672

European-Non Finnish (NFE)

AF:

0.00261

AC:

2899

AN:

1111194

Other (OTH)

AF:

0.0362

AC:

2179

AN:

60182

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

824

1647

2471

3294

4118

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

344

688

1032

1376

1720

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0240

AC:

3655

AN:

152290

Hom.:

664

Cov.:

AF XY:

0.0271

AC XY:

2015

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.00361

AC:

150

AN:

41586

American (AMR)

AF:

0.00673

AC:

103

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00461

AC:

AN:

3472

East Asian (EAS)

AF:

0.498

AC:

2551

AN:

5118

South Asian (SAS)

AF:

0.0308

AC:

149

AN:

4832

European-Finnish (FIN)

AF:

0.0348

AC:

370

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00394

AC:

268

AN:

68030

Other (OTH)

AF:

0.0227

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

131

262

394

525

656

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

162

216

270

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00447

Hom.:

Bravo

AF:

0.0242

Asia WGS

AF:

0.217

AC:

752

AN:

3478

EpiCase

AF:

0.00305

EpiControl

AF:

0.00214

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

1.0

(source)

DANN

Benign

0.59

PhyloP100

-0.53

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over