rs375540118

Variant names:

• chr17-80994662-C-A
• rs375540118
• NM_024591.5:c.145C>A

Your query was ambiguous. Multiple possible variants found:

• chr17-80994662-C-A
• chr17-80994662-C-T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_024591.5(CHMP6):​c.145C>A​(p.Arg49Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000021 in 1,427,606 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CHMP6 NM_024591.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.236
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.26).
• BP7: Synonymous conserved (PhyloP=0.236 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHMP6	NM_024591.5	c.145C>A	p.Arg49Arg	synonymous_variant	Exon 2 of 8	ENST00000325167.9	NP_078867.2
CHMP6	XM_005257668.1	c.145C>A	p.Arg49Arg	synonymous_variant	Exon 2 of 7		XP_005257725.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHMP6	ENST00000325167.9	c.145C>A	p.Arg49Arg	synonymous_variant	Exon 2 of 8	1	NM_024591.5	ENSP00000317468.5
CHMP6	ENST00000572778.5	c.82C>A	p.Arg28Arg	synonymous_variant	Exon 1 of 6	2		ENSP00000461098.1
CHMP6	ENST00000571457.1	c.19C>A	p.Arg7Arg	synonymous_variant	Exon 1 of 7	3		ENSP00000461238.1
CHMP6	ENST00000572525.5	c.-114C>A		5_prime_UTR_variant	Exon 2 of 8	3		ENSP00000460389.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000547 AC: 1 AN: 182894 AF XY: 0.0000101

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000130

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000210 AC: 3 AN: 1427606 Hom.: 0 Cov.: 31 AF XY: 0.00000424 AC XY: 3 AN XY: 706918

African (AFR) AF: 0.00 AC: 0 AN: 32856

American (AMR) AF: 0.00 AC: 0 AN: 38710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25376

East Asian (EAS) AF: 0.00 AC: 0 AN: 38284

South Asian (SAS) AF: 0.00 AC: 0 AN: 81190

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49298

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5718

European-Non Finnish (NFE) AF: 0.00000273 AC: 3 AN: 1096970

Other (OTH) AF: 0.00 AC: 0 AN: 59204

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
CADD	Benign	9.0
DANN	Benign	0.90
PhyloP100		0.24
PromoterAI		-0.0059	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs375540118; hg19: chr17-78968462;