rs1049341

Variant names:

• chr10-17237563-G-T
• rs1049341
• NM_003380.5:c.*292G>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003380.5(VIM):​c.*292G>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 0.142 in 329,654 control chromosomes in the GnomAD database, including 7,943 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (6193 hom., cov: 32)
  • Exomes 𝑓: 0.088 (1750 hom.)
• Consequence: VIM NM_003380.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.30
• Publications: 6 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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 10-17237563-G-T is Benign according to our data. Variant chr10-17237563-G-T is described in ClinVar as Benign. ClinVar VariationId is 1283433.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.502 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VIM	NM_003380.5	c.*292G>T		3_prime_UTR_variant	Exon 10 of 10	ENST00000544301.7	NP_003371.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VIM	ENST00000544301.7	c.*292G>T		3_prime_UTR_variant	Exon 10 of 10	1	NM_003380.5	ENSP00000446007.1

Frequencies

GnomAD3 genomes AF: 0.204 AC: 30929 AN: 151712 Hom.: 6159 Cov.: 32

Gnomad AFR AF: 0.508

Gnomad AMI AF: 0.0890

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.0392

Gnomad EAS AF: 0.211

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0372

Gnomad OTH AF: 0.152

GnomAD4 exome AF: 0.0880 AC: 15643 AN: 177824 Hom.: 1750 Cov.: 0 AF XY: 0.0850 AC XY: 7895 AN XY: 92846

African (AFR) AF: 0.513 AC: 2823 AN: 5500

American (AMR) AF: 0.285 AC: 2085 AN: 7324

Ashkenazi Jewish (ASJ) AF: 0.0376 AC: 230 AN: 6112

East Asian (EAS) AF: 0.204 AC: 2735 AN: 13400

South Asian (SAS) AF: 0.0926 AC: 1071 AN: 11562

European-Finnish (FIN) AF: 0.147 AC: 1363 AN: 9282

Middle Eastern (MID) AF: 0.0399 AC: 31 AN: 776

European-Non Finnish (NFE) AF: 0.0367 AC: 4135 AN: 112684

Other (OTH) AF: 0.105 AC: 1170 AN: 11184

GnomAD4 genome AF: 0.204 AC: 31024 AN: 151830 Hom.: 6193 Cov.: 32 AF XY: 0.209 AC XY: 15500 AN XY: 74184

African (AFR) AF: 0.508 AC: 21025 AN: 41372

American (AMR) AF: 0.241 AC: 3679 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.0392 AC: 136 AN: 3472

East Asian (EAS) AF: 0.210 AC: 1088 AN: 5170

South Asian (SAS) AF: 0.108 AC: 520 AN: 4818

European-Finnish (FIN) AF: 0.156 AC: 1631 AN: 10482

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0372 AC: 2530 AN: 67940

Other (OTH) AF: 0.150 AC: 318 AN: 2114

Alfa AF: 0.0726 Hom.: 1517

Bravo AF: 0.228

Asia WGS AF: 0.196 AC: 681 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jul 21, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	11
DANN	Benign	0.49
PhyloP100		3.3
Mutation Taster		=100/0	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: rs1049341; hg19: chr10-17279562;