rs3249

Positions:

• chr10-17237518-C-T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4 BP6_Very_Strong BA1

The NM_003380.5(VIM):​c.*247C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 452,060 control chromosomes in the GnomAD database, including 11,689 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (3210 hom., cov: 32)
  • Exomes 𝑓: 0.23 (8479 hom.)
• Consequence: VIM NM_003380.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.658

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]

ACMG classification

Verdict is Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.17).
• BP6: Variant 10-17237518-C-T is Benign according to our data. Variant chr10-17237518-C-T is described in ClinVar as [Benign]. Clinvar id is 1288184.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VIM	NM_003380.5	c.*247C>T		3_prime_UTR_variant	10/10	ENST00000544301.7	NP_003371.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VIM	ENST00000544301.7	c.*247C>T		3_prime_UTR_variant	10/10	1	NM_003380.5	ENSP00000446007.1

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28533 AN: 151824 Hom.: 3208 Cov.: 32

Gnomad AFR AF: 0.0806

Gnomad AMI AF: 0.350

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.0738

Gnomad SAS AF: 0.0903

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.151

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.186

GnomAD4 exome AF: 0.225 AC: 67651 AN: 300116 Hom.: 8479 Cov.: 4 AF XY: 0.222 AC XY: 34830 AN XY: 156556

Gnomad4 AFR exome AF: 0.0816

Gnomad4 AMR exome AF: 0.148

Gnomad4 ASJ exome AF: 0.153

Gnomad4 EAS exome AF: 0.0627

Gnomad4 SAS exome AF: 0.106

Gnomad4 FIN exome AF: 0.221

Gnomad4 NFE exome AF: 0.275

Gnomad4 OTH exome AF: 0.215

GnomAD4 genome AF: 0.188 AC: 28538 AN: 151944 Hom.: 3210 Cov.: 32 AF XY: 0.182 AC XY: 13545 AN XY: 74280

Gnomad4 AFR AF: 0.0803

Gnomad4 AMR AF: 0.173

Gnomad4 ASJ AF: 0.162

Gnomad4 EAS AF: 0.0737

Gnomad4 SAS AF: 0.0908

Gnomad4 FIN AF: 0.215

Gnomad4 NFE AF: 0.267

Gnomad4 OTH AF: 0.189

Alfa AF: 0.246 Hom.: 4684

Bravo AF: 0.181

Asia WGS AF: 0.116 AC: 400 AN: 3460

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 28, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.17
CADD	Benign	13
DANN	Benign	0.79
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs3249; hg19: chr10-17279517;