rs1049341

Positions:

• chr10-17237563-G-T

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.*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

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 -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 id 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/exons	MANE	Protein	UniProt
VIM	NM_003380.5	c.*292G>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.*292G>T		3_prime_UTR_variant	10/10	1	NM_003380.5	ENSP00000446007	P1
VIM	ENST00000224237.9	c.*292G>T		3_prime_UTR_variant	9/9	1		ENSP00000224237	P1
VIM	ENST00000469543.5	c.*1320G>T		3_prime_UTR_variant, NMD_transcript_variant	6/6	2		ENSP00000431702
VIM	ENST00000487938.5	c.*801G>T		3_prime_UTR_variant, NMD_transcript_variant	8/8	5		ENSP00000435613

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

Gnomad4 AFR exome AF: 0.513

Gnomad4 AMR exome AF: 0.285

Gnomad4 ASJ exome AF: 0.0376

Gnomad4 EAS exome AF: 0.204

Gnomad4 SAS exome AF: 0.0926

Gnomad4 FIN exome AF: 0.147

Gnomad4 NFE exome AF: 0.0367

Gnomad4 OTH exome AF: 0.105

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

Gnomad4 AFR AF: 0.508

Gnomad4 AMR AF: 0.241

Gnomad4 ASJ AF: 0.0392

Gnomad4 EAS AF: 0.210

Gnomad4 SAS AF: 0.108

Gnomad4 FIN AF: 0.156

Gnomad4 NFE AF: 0.0372

Gnomad4 OTH AF: 0.150

Alfa AF: 0.0666 Hom.: 1171

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 21, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	11
DANN	Benign	0.49

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: rs1049341; hg19: chr10-17279562;