chr11-61138978-A-G

Position:

• chr11-61138978-A-G

Variant summary

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

The NM_017966.5(VPS37C):​c.-6-143T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.605 in 726,456 control chromosomes in the GnomAD database, including 142,491 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 0.65 (34260 hom., cov: 31)
  • Exomes 𝑓: 0.59 (108231 hom.)
• Consequence: VPS37C NM_017966.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.128

Genes affected

VPS37C (HGNC:26097): (VPS37C subunit of ESCRT-I) VPS37C is a subunit of ESCRT-I (endosomal sorting complex required for transport I), a complex in the class E vacuolar protein sorting (VPS) pathway required for sorting ubiquitinated transmembrane proteins into internal vesicles of multivesicular bodies (Eastman et al., 2005 [PubMed 15509564]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VPS37C	NM_017966.5	c.-6-143T>C		intron_variant		ENST00000301765.10	NP_060436.4
VPS37C	XM_005274077.4	c.-6-143T>C		intron_variant			XP_005274134.1
VPS37C	XM_047427178.1	c.-6-143T>C		intron_variant			XP_047283134.1
VPS37C	XM_047427179.1	c.-6-143T>C		intron_variant			XP_047283135.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VPS37C	ENST00000301765.10	c.-6-143T>C		intron_variant		1	NM_017966.5	ENSP00000301765	P1
VPS37C	ENST00000538036.1	c.-6-143T>C		intron_variant		2		ENSP00000446013
VPS37C	ENST00000535818.1	n.226-143T>C		intron_variant, non_coding_transcript_variant		2
VPS37C	ENST00000536000.1	n.64-143T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.653 AC: 99236 AN: 151922 Hom.: 34205 Cov.: 31

Gnomad AFR AF: 0.829

Gnomad AMI AF: 0.489

Gnomad AMR AF: 0.666

Gnomad ASJ AF: 0.563

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.837

Gnomad FIN AF: 0.626

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.517

Gnomad OTH AF: 0.616

GnomAD4 exome AF: 0.592 AC: 340165 AN: 574416 Hom.: 108231 AF XY: 0.602 AC XY: 181743 AN XY: 302070

Gnomad4 AFR exome AF: 0.834

Gnomad4 AMR exome AF: 0.720

Gnomad4 ASJ exome AF: 0.554

Gnomad4 EAS exome AF: 0.999

Gnomad4 SAS exome AF: 0.804

Gnomad4 FIN exome AF: 0.601

Gnomad4 NFE exome AF: 0.506

Gnomad4 OTH exome AF: 0.589

GnomAD4 genome AF: 0.653 AC: 99354 AN: 152040 Hom.: 34260 Cov.: 31 AF XY: 0.662 AC XY: 49149 AN XY: 74298

Gnomad4 AFR AF: 0.829

Gnomad4 AMR AF: 0.667

Gnomad4 ASJ AF: 0.563

Gnomad4 EAS AF: 0.997

Gnomad4 SAS AF: 0.835

Gnomad4 FIN AF: 0.626

Gnomad4 NFE AF: 0.517

Gnomad4 OTH AF: 0.621

Alfa AF: 0.591 Hom.: 3456

Bravo AF: 0.661

Asia WGS AF: 0.911 AC: 3167 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.7
DANN	Benign	0.47

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: rs508970; hg19: chr11-60906450;