rs4903

Variant names:

• chr10-17233862-C-T
• rs4903
• NM_003380.5:c.813C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_003380.5(VIM):​c.813C>T​(p.Asp271Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00974 in 1,614,042 control chromosomes in the GnomAD database, including 1,147 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.049 (576 hom., cov: 33)
  • Exomes 𝑓: 0.0057 (571 hom.)
• Consequence: VIM NM_003380.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.28
• Publications: 7 publications found

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 Gene-Disease associations (from GenCC):

• cataract

  Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
• cataract 30

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• pulverulent cataract

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000234961 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 10-17233862-C-T is Benign according to our data. Variant chr10-17233862-C-T is described in ClinVar as Benign. ClinVar VariationId is 474044.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.28 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003380.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VIM	NM_003380.5	MANE Select	c.813C>T	p.Asp271Asp	synonymous	Exon 5 of 10	NP_003371.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VIM	ENST00000544301.7	TSL:1 MANE Select	c.813C>T	p.Asp271Asp	synonymous	Exon 5 of 10	ENSP00000446007.1
	VIM	ENST00000224237.9	TSL:1	c.813C>T	p.Asp271Asp	synonymous	Exon 4 of 9	ENSP00000224237.5
	VIM	ENST00000421459.2	TSL:2	n.291C>T		non_coding_transcript_exon	Exon 3 of 4

Frequencies

GnomAD3 genomes AF: 0.0488 AC: 7419 AN: 152048 Hom.: 576 Cov.: 33

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0165

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00560

Gnomad SAS AF: 0.00954

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000647

Gnomad OTH AF: 0.0364

GnomAD2 exomes AF: 0.0139 AC: 3484 AN: 251408 AF XY: 0.0104

Gnomad AFR exome AF: 0.169

Gnomad AMR exome AF: 0.00778

Gnomad ASJ exome AF: 0.000694

Gnomad EAS exome AF: 0.00549

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000703

Gnomad OTH exome AF: 0.00684

GnomAD4 exome AF: 0.00567 AC: 8293 AN: 1461876 Hom.: 571 Cov.: 31 AF XY: 0.00510 AC XY: 3711 AN XY: 727236

African (AFR) AF: 0.175 AC: 5856 AN: 33478

American (AMR) AF: 0.00937 AC: 419 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000383 AC: 10 AN: 26136

East Asian (EAS) AF: 0.00249 AC: 99 AN: 39698

South Asian (SAS) AF: 0.00713 AC: 615 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.0137 AC: 79 AN: 5768

European-Non Finnish (NFE) AF: 0.000458 AC: 509 AN: 1111998

Other (OTH) AF: 0.0117 AC: 706 AN: 60396

GnomAD4 genome AF: 0.0488 AC: 7428 AN: 152166 Hom.: 576 Cov.: 33 AF XY: 0.0474 AC XY: 3527 AN XY: 74394

African (AFR) AF: 0.168 AC: 6978 AN: 41486

American (AMR) AF: 0.0165 AC: 252 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00562 AC: 29 AN: 5164

South Asian (SAS) AF: 0.00954 AC: 46 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000647 AC: 44 AN: 68014

Other (OTH) AF: 0.0360 AC: 76 AN: 2112

Alfa AF: 0.0246 Hom.: 184

Bravo AF: 0.0546

Asia WGS AF: 0.0190 AC: 66 AN: 3478

EpiCase AF: 0.000600

EpiControl AF: 0.000889

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Cataract 30 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	5.9
DANN	Benign	0.79
PhyloP100		-1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=98/2	polymorphism (auto)

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: rs4903; hg19: chr10-17275861;