chr10-17237518-C-T

Variant names:

• chr10-17237518-C-T
• rs3249
• NM_003380.5:c.*247C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 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 -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 VariationId 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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VIM	NM_003380.5	MANE Select	c.*247C>T		3_prime_UTR	Exon 10 of 10	NP_003371.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VIM	ENST00000544301.7	TSL:1 MANE Select	c.*247C>T		3_prime_UTR	Exon 10 of 10	ENSP00000446007.1
	VIM	ENST00000224237.9	TSL:1	c.*247C>T		3_prime_UTR	Exon 9 of 9	ENSP00000224237.5
	VIM	ENST00000946784.1		c.*247C>T		3_prime_UTR	Exon 10 of 10	ENSP00000616843.1

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

African (AFR) AF: 0.0816 AC: 688 AN: 8434

American (AMR) AF: 0.148 AC: 1596 AN: 10764

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 1469 AN: 9628

East Asian (EAS) AF: 0.0627 AC: 1446 AN: 23058

South Asian (SAS) AF: 0.106 AC: 2063 AN: 19404

European-Finnish (FIN) AF: 0.221 AC: 4966 AN: 22460

Middle Eastern (MID) AF: 0.128 AC: 177 AN: 1388

European-Non Finnish (NFE) AF: 0.275 AC: 51360 AN: 186916

Other (OTH) AF: 0.215 AC: 3886 AN: 18064

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

African (AFR) AF: 0.0803 AC: 3333 AN: 41488

American (AMR) AF: 0.173 AC: 2635 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 563 AN: 3470

East Asian (EAS) AF: 0.0737 AC: 382 AN: 5180

South Asian (SAS) AF: 0.0908 AC: 438 AN: 4824

European-Finnish (FIN) AF: 0.215 AC: 2260 AN: 10504

Middle Eastern (MID) AF: 0.151 AC: 44 AN: 292

European-Non Finnish (NFE) AF: 0.267 AC: 18168 AN: 67920

Other (OTH) AF: 0.189 AC: 399 AN: 2110

Alfa AF: 0.245 Hom.: 5615

Bravo AF: 0.181

Asia WGS AF: 0.116 AC: 400 AN: 3460

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.17
CADD	Benign	13
DANN	Benign	0.79
PhyloP100		0.66
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs3249; hg19: chr10-17279517;