10-17229401-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003380.5(VIM):c.-22G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 1,587,024 control chromosomes in the GnomAD database, including 92,116 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.41 (14765 hom., cov: 32)
  • Exomes 𝑓: 0.32 (77351 hom.)
• Consequence: VIM NM_003380.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.09

Genes affected

VIM (HGNC:12692): (vimentin) This gene encodes a type III intermediate filament protein. Intermediate filaments, along with microtubules and actin microfilaments, make up the cytoskeleton. The encoded protein is responsible for maintaining cell shape and integrity of the cytoplasm, and stabilizing cytoskeletal interactions. This protein is involved in neuritogenesis and cholesterol transport and functions as an organizer of a number of other critical proteins involved in cell attachment, migration, and signaling. Bacterial and viral pathogens have been shown to attach to this protein on the host cell surface. Mutations in this gene are associated with congenital cataracts in human patients. [provided by RefSeq, Aug 2017]

VIM-AS1 (HGNC:44879): (VIM antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 10-17229401-G-C is Benign according to our data. Variant chr10-17229401-G-C is described in ClinVar as [Benign]. Clinvar id is 1277763.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VIM	NM_003380.5	c.-22G>C		5_prime_UTR_variant	2/10	ENST00000544301.7
VIM-AS1	NR_108061.1	n.585C>G		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VIM	ENST00000544301.7	c.-22G>C		5_prime_UTR_variant	2/10	1	NM_003380.5	P1
VIM-AS1	ENST00000605833.2	n.618C>G		non_coding_transcript_exon_variant	1/3	3

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62814 AN: 151762 Hom.: 14721 Cov.: 32

Gnomad AFR AF: 0.644

Gnomad AMI AF: 0.444

Gnomad AMR AF: 0.423

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.282

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.373

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.360

GnomAD3 exomes AF: 0.344 AC: 70253 AN: 204226 Hom.: 13287 AF XY: 0.328 AC XY: 36988 AN XY: 112870

Gnomad AFR exome AF: 0.654

Gnomad AMR exome AF: 0.479

Gnomad ASJ exome AF: 0.191

Gnomad EAS exome AF: 0.282

Gnomad SAS exome AF: 0.234

Gnomad FIN exome AF: 0.367

Gnomad NFE exome AF: 0.314

Gnomad OTH exome AF: 0.315

GnomAD4 exome AF: 0.321 AC: 460557 AN: 1435150 Hom.: 77351 Cov.: 34 AF XY: 0.316 AC XY: 225679 AN XY: 713324

Gnomad4 AFR exome AF: 0.656

Gnomad4 AMR exome AF: 0.470

Gnomad4 ASJ exome AF: 0.187

Gnomad4 EAS exome AF: 0.262

Gnomad4 SAS exome AF: 0.234

Gnomad4 FIN exome AF: 0.363

Gnomad4 NFE exome AF: 0.316

Gnomad4 OTH exome AF: 0.322

GnomAD4 genome AF: 0.414 AC: 62918 AN: 151874 Hom.: 14765 Cov.: 32 AF XY: 0.414 AC XY: 30696 AN XY: 74222

Gnomad4 AFR AF: 0.644

Gnomad4 AMR AF: 0.424

Gnomad4 ASJ AF: 0.203

Gnomad4 EAS AF: 0.282

Gnomad4 SAS AF: 0.241

Gnomad4 FIN AF: 0.373

Gnomad4 NFE AF: 0.313

Gnomad4 OTH AF: 0.361

Alfa AF: 0.251 Hom.: 914

Bravo AF: 0.432

Asia WGS AF: 0.322 AC: 1119 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 29, 2018

- -

Cataract 30 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	11
Dann	Benign	0.81

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: rs3758410; hg19: chr10-17271400; COSMIC: COSV56407419; COSMIC: COSV56407419;