10-17229111-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003380.5(VIM):c.-147-165G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 465,302 control chromosomes in the GnomAD database, including 15,023 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.24 (5147 hom., cov: 32)
  • Exomes 𝑓: 0.22 (9876 hom.)
• Consequence: VIM NM_003380.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0570

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-AS1 (HGNC:44879): (VIM antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 10-17229111-G-C is Benign according to our data. Variant chr10-17229111-G-C is described in ClinVar as [Benign]. Clinvar id is 1246121.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.351 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VIM	NM_003380.5	c.-147-165G>C		intron_variant		ENST00000544301.7
VIM-AS1	NR_108061.1	n.641+234C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VIM	ENST00000544301.7	c.-147-165G>C		intron_variant		1	NM_003380.5	P1
VIM-AS1	ENST00000605833.2	n.674+234C>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36321 AN: 151388 Hom.: 5136 Cov.: 32

Gnomad AFR AF: 0.0928

Gnomad AMI AF: 0.428

Gnomad AMR AF: 0.358

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.290

Gnomad OTH AF: 0.238

GnomAD4 exome AF: 0.218 AC: 68263 AN: 313800 Hom.: 9876 Cov.: 0 AF XY: 0.211 AC XY: 35005 AN XY: 166104

Gnomad4 AFR exome AF: 0.0534

Gnomad4 AMR exome AF: 0.331

Gnomad4 ASJ exome AF: 0.120

Gnomad4 EAS exome AF: 0.182

Gnomad4 SAS exome AF: 0.145

Gnomad4 FIN exome AF: 0.284

Gnomad4 NFE exome AF: 0.236

Gnomad4 OTH exome AF: 0.208

GnomAD4 genome AF: 0.240 AC: 36349 AN: 151502 Hom.: 5147 Cov.: 32 AF XY: 0.243 AC XY: 17978 AN XY: 73962

Gnomad4 AFR AF: 0.0928

Gnomad4 AMR AF: 0.359

Gnomad4 ASJ AF: 0.183

Gnomad4 EAS AF: 0.270

Gnomad4 SAS AF: 0.164

Gnomad4 FIN AF: 0.346

Gnomad4 NFE AF: 0.290

Gnomad4 OTH AF: 0.241

Alfa AF: 0.263 Hom.: 705

Bravo AF: 0.239

Asia WGS AF: 0.242 AC: 841 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	-0.83
Cadd	Benign	1.2
Dann	Benign	0.77
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: rs3758411; hg19: chr10-17271110;