18-11852183-C-T

Position:

• chr18-11852183-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020412.5(CHMP1B):​c.*72C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 1,456,364 control chromosomes in the GnomAD database, including 19,344 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.11 (1348 hom., cov: 33)
  • Exomes 𝑓: 0.16 (17996 hom.)
• Consequence: CHMP1B NM_020412.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.690

Genes affected

CHMP1B (HGNC:24287): (charged multivesicular body protein 1B) CHMP1B belongs to the chromatin-modifying protein/charged multivesicular body protein (CHMP) family. These proteins are components of ESCRT-III (endosomal sorting complex required for transport III), a complex involved in degradation of surface receptor proteins and formation of endocytic multivesicular bodies (MVBs). Some CHMPs have both nuclear and cytoplasmic/vesicular distributions, and one such CHMP, CHMP1A (MIM 164010), is required for both MVB formation and regulation of cell cycle progression (Tsang et al., 2006 [PubMed 16730941]).[supplied by OMIM, Mar 2008]

GNAL (HGNC:4388): (G protein subunit alpha L) This gene encodes a stimulatory G protein alpha subunit which mediates odorant signaling in the olfactory epithelium. This protein couples dopamine type 1 receptors and adenosine A2A receptors and is widely expressed in the central nervous system. Mutations in this gene have been associated with dystonia 25 and this gene is located in a susceptibility region for bipolar disorder and schizophrenia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]

CHMP1B-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHMP1B	NM_020412.5	c.*72C>T		3_prime_UTR_variant	1/1	ENST00000526991.3	NP_065145.2
GNAL	NM_182978.4	c.723-10212C>T		intron_variant		ENST00000334049.11	NP_892023.1
GNAL	NM_001369387.1	c.492-10212C>T		intron_variant		ENST00000423027.8	NP_001356316.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHMP1B	ENST00000526991.3	c.*72C>T		3_prime_UTR_variant	1/1	6	NM_020412.5	ENSP00000432279.1
GNAL	ENST00000334049.11	c.723-10212C>T		intron_variant		1	NM_182978.4	ENSP00000334051.5
GNAL	ENST00000423027.8	c.492-10212C>T		intron_variant		1	NM_001369387.1	ENSP00000408489.2

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17306 AN: 152152 Hom.: 1347 Cov.: 33

Gnomad AFR AF: 0.0306

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.0875

Gnomad ASJ AF: 0.0896

Gnomad EAS AF: 0.0175

Gnomad SAS AF: 0.0546

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.114

GnomAD4 exome AF: 0.160 AC: 208365 AN: 1304094 Hom.: 17996 Cov.: 26 AF XY: 0.157 AC XY: 99888 AN XY: 634374

Gnomad4 AFR exome AF: 0.0244

Gnomad4 AMR exome AF: 0.0787

Gnomad4 ASJ exome AF: 0.0872

Gnomad4 EAS exome AF: 0.0243

Gnomad4 SAS exome AF: 0.0576

Gnomad4 FIN exome AF: 0.192

Gnomad4 NFE exome AF: 0.178

Gnomad4 OTH exome AF: 0.135

GnomAD4 genome AF: 0.114 AC: 17300 AN: 152270 Hom.: 1348 Cov.: 33 AF XY: 0.111 AC XY: 8283 AN XY: 74446

Gnomad4 AFR AF: 0.0305

Gnomad4 AMR AF: 0.0872

Gnomad4 ASJ AF: 0.0896

Gnomad4 EAS AF: 0.0176

Gnomad4 SAS AF: 0.0549

Gnomad4 FIN AF: 0.184

Gnomad4 NFE AF: 0.172

Gnomad4 OTH AF: 0.112

Alfa AF: 0.147 Hom.: 2124

Bravo AF: 0.104

Asia WGS AF: 0.0450 AC: 157 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.0
DANN	Benign	0.62

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: rs1786581; hg19: chr18-11852182;