17-80999674-T-C

Position:

• chr17-80999674-T-C

Variant summary

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

The NM_024591.5(CHMP6):​c.*521T>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 0.335 in 154,150 control chromosomes in the GnomAD database, including 10,020 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 0.33 (9865 hom., cov: 33)
  • Exomes 𝑓: 0.37 (155 hom.)
• Consequence: CHMP6 NM_024591.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.29

Genes affected

CHMP6 (HGNC:25675): (charged multivesicular body protein 6) This gene encodes a member of the chromatin-modifying protein/charged multivesicular body protein family. Proteins in this family are part of the ESCRT-III (endosomal sorting complex required for transport III) which degrades surface receptors, and in biosynthesis of endosomes. [provided by RefSeq, Mar 2012]

ENSG00000263218 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.426 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHMP6	NM_024591.5	c.*521T>C		3_prime_UTR_variant	8/8	ENST00000325167.9	NP_078867.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHMP6	ENST00000325167.9	c.*521T>C		3_prime_UTR_variant	8/8	1	NM_024591.5	ENSP00000317468.5
CHMP6	ENST00000571457.1	c.424+1254T>C		intron_variant		3		ENSP00000461238.1
ENSG00000263218	ENST00000576215.1	n.305-132A>G		intron_variant		3
ENSG00000263218	ENST00000577061.2	n.144-15A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50937 AN: 152076 Hom.: 9863 Cov.: 33

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.667

Gnomad AMR AF: 0.434

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.393

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.425

Gnomad OTH AF: 0.349

GnomAD4 exome AF: 0.371 AC: 725 AN: 1954 Hom.: 155 Cov.: 0 AF XY: 0.347 AC XY: 346 AN XY: 996

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.420

Gnomad4 ASJ exome AF: 0.214

Gnomad4 EAS exome AF: 0.269

Gnomad4 SAS exome AF: 0.278

Gnomad4 FIN exome AF: 0.342

Gnomad4 NFE exome AF: 0.393

Gnomad4 OTH exome AF: 0.302

GnomAD4 genome AF: 0.335 AC: 50949 AN: 152196 Hom.: 9865 Cov.: 33 AF XY: 0.332 AC XY: 24698 AN XY: 74398

Gnomad4 AFR AF: 0.129

Gnomad4 AMR AF: 0.435

Gnomad4 ASJ AF: 0.369

Gnomad4 EAS AF: 0.393

Gnomad4 SAS AF: 0.341

Gnomad4 FIN AF: 0.345

Gnomad4 NFE AF: 0.425

Gnomad4 OTH AF: 0.349

Alfa AF: 0.411 Hom.: 10533

Bravo AF: 0.335

Asia WGS AF: 0.348 AC: 1213 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.6
DANN	Benign	0.32
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs1128687; hg19: chr17-78973474;