rs6860

Positions:

• chr16-89644712-C-T

Variant summary

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

The NM_002768.5(CHMP1A):​c.*1354G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 152,246 control chromosomes in the GnomAD database, including 10,112 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 0.32 (10103 hom., cov: 33)
  • Exomes 𝑓: 0.40 (9 hom.)
• Consequence: CHMP1A NM_002768.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHMP1A	NM_002768.5	c.*1354G>A		3_prime_UTR_variant	7/7	ENST00000397901.8
CHMP1A	NM_001083314.4	c.*1202G>A		3_prime_UTR_variant	6/6
CHMP1A	XM_047434195.1	c.*1354G>A		3_prime_UTR_variant	7/7
CHMP1A	NR_046418.3	n.2233G>A		non_coding_transcript_exon_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHMP1A	ENST00000397901.8	c.*1354G>A		3_prime_UTR_variant	7/7	1	NM_002768.5	P1

Frequencies

GnomAD3 genomes AF: 0.319 AC: 48563 AN: 152018 Hom.: 10103 Cov.: 33

Gnomad AFR AF: 0.0838

Gnomad AMI AF: 0.613

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.551

Gnomad EAS AF: 0.0200

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.385

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.452

Gnomad OTH AF: 0.410

GnomAD4 exome AF: 0.400 AC: 44 AN: 110 Hom.: 9 Cov.: 0 AF XY: 0.461 AC XY: 35 AN XY: 76

Gnomad4 AMR exome AF: 0.500

Gnomad4 FIN exome AF: 0.333

Gnomad4 NFE exome AF: 0.419

Gnomad4 OTH exome AF: 0.375

GnomAD4 genome AF: 0.319 AC: 48555 AN: 152136 Hom.: 10103 Cov.: 33 AF XY: 0.314 AC XY: 23380 AN XY: 74368

Gnomad4 AFR AF: 0.0836

Gnomad4 AMR AF: 0.364

Gnomad4 ASJ AF: 0.551

Gnomad4 EAS AF: 0.0199

Gnomad4 SAS AF: 0.232

Gnomad4 FIN AF: 0.385

Gnomad4 NFE AF: 0.452

Gnomad4 OTH AF: 0.406

Alfa AF: 0.454 Hom.: 14008

Bravo AF: 0.310

Asia WGS AF: 0.136 AC: 474 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.1
DANN	Benign	0.47
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs6860; hg19: chr16-89711120;