17-81000101-C-G

Variant names:

• chr17-81000101-C-G
• rs1128705
• NM_024591.5:c.*948C>G

Variant summary

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

The NM_024591.5(CHMP6):​c.*948C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 152,118 control chromosomes in the GnomAD database, including 11,184 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 0.38 (11183 hom., cov: 33)
  • Exomes 𝑓: 0.33 (1 hom.)
• Consequence: CHMP6 NM_024591.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.550

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.443 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHMP6	NM_024591.5	c.*948C>G		3_prime_UTR_variant	Exon 8 of 8	ENST00000325167.9	NP_078867.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHMP6	ENST00000325167.9	c.*948C>G		3_prime_UTR_variant	Exon 8 of 8	1	NM_024591.5	ENSP00000317468.5
CHMP6	ENST00000571457.1	c.424+1681C>G		intron_variant	Intron 6 of 6	3		ENSP00000461238.1
ENSG00000263218	ENST00000576215.1	n.30G>C		non_coding_transcript_exon_variant	Exon 1 of 2	3
ENSG00000263218	ENST00000577061.2	n.27G>C		non_coding_transcript_exon_variant	Exon 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.376 AC: 57191 AN: 151966 Hom.: 11178 Cov.: 33

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.667

Gnomad AMR AF: 0.452

Gnomad ASJ AF: 0.372

Gnomad EAS AF: 0.392

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.375

GnomAD4 exome AF: 0.333 AC: 10 AN: 30 Hom.: 1 Cov.: 0 AF XY: 0.300 AC XY: 6 AN XY: 20

Gnomad4 AFR exome AF: 0.00

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.250

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.376 AC: 57231 AN: 152088 Hom.: 11183 Cov.: 33 AF XY: 0.372 AC XY: 27682 AN XY: 74356

Gnomad4 AFR AF: 0.276

Gnomad4 AMR AF: 0.452

Gnomad4 ASJ AF: 0.372

Gnomad4 EAS AF: 0.391

Gnomad4 SAS AF: 0.339

Gnomad4 FIN AF: 0.340

Gnomad4 NFE AF: 0.424

Gnomad4 OTH AF: 0.375

Alfa AF: 0.257 Hom.: 628

Bravo AF: 0.384

Asia WGS AF: 0.356 AC: 1241 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.62
DANN	Benign	0.44

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: rs1128705; hg19: chr17-78973901;