18-11852183-C-T

Variant names:

• chr18-11852183-C-T
• rs1786581
• NM_020412.5:c.*72C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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:52778): (CHMP1B antisense RNA 1)

ENSG00000296678 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020412.5. 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
	CHMP1B	NM_020412.5	MANE Select	c.*72C>T		3_prime_UTR	Exon 1 of 1	NP_065145.2
	GNAL	NM_182978.4	MANE Select	c.723-10212C>T		intron	N/A	NP_892023.1	P38405-2
	GNAL	NM_001369387.1	MANE Plus Clinical	c.492-10212C>T		intron	N/A	NP_001356316.1	A8K1Y9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHMP1B	ENST00000526991.3	TSL:6 MANE Select	c.*72C>T		3_prime_UTR	Exon 1 of 1	ENSP00000432279.1	Q7LBR1
	GNAL	ENST00000334049.11	TSL:1 MANE Select	c.723-10212C>T		intron	N/A	ENSP00000334051.5	P38405-2
	GNAL	ENST00000423027.8	TSL:1 MANE Plus Clinical	c.492-10212C>T		intron	N/A	ENSP00000408489.2	P38405-1

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

African (AFR) AF: 0.0244 AC: 699 AN: 28632

American (AMR) AF: 0.0787 AC: 1766 AN: 22444

Ashkenazi Jewish (ASJ) AF: 0.0872 AC: 1691 AN: 19400

East Asian (EAS) AF: 0.0243 AC: 852 AN: 34994

South Asian (SAS) AF: 0.0576 AC: 3716 AN: 64544

European-Finnish (FIN) AF: 0.192 AC: 8843 AN: 45940

Middle Eastern (MID) AF: 0.0947 AC: 449 AN: 4740

European-Non Finnish (NFE) AF: 0.178 AC: 183097 AN: 1029564

Other (OTH) AF: 0.135 AC: 7252 AN: 53836

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

African (AFR) AF: 0.0305 AC: 1266 AN: 41570

American (AMR) AF: 0.0872 AC: 1334 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0896 AC: 311 AN: 3472

East Asian (EAS) AF: 0.0176 AC: 91 AN: 5178

South Asian (SAS) AF: 0.0549 AC: 265 AN: 4830

European-Finnish (FIN) AF: 0.184 AC: 1954 AN: 10592

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.172 AC: 11675 AN: 68014

Other (OTH) AF: 0.112 AC: 237 AN: 2114

Alfa AF: 0.141 Hom.: 2795

Bravo AF: 0.104

Asia WGS AF: 0.0450 AC: 157 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.0
DANN	Benign	0.62
PhyloP100		-0.69
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: rs1786581; hg19: chr18-11852182;