NM_003380.5:c.-147-165G>C

Variant names:

• chr10-17229111-G-C
• rs3758411
• NM_003380.5:c.-147-165G>C

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.-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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0570
• Publications: 5 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-AS1 (HGNC:44879): (VIM antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 1246121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.351 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.-147-165G>C		intron	N/A	NP_003371.2	P08670
	VIM-AS1	NR_108061.1		n.641+234C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VIM	ENST00000544301.7	TSL:1 MANE Select	c.-147-165G>C		intron	N/A	ENSP00000446007.1	P08670
	VIM	ENST00000881961.1		c.-312G>C		5_prime_UTR	Exon 1 of 9	ENSP00000552020.1
	VIM	ENST00000946784.1		c.-124-188G>C		intron	N/A	ENSP00000616843.1

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

African (AFR) AF: 0.0534 AC: 402 AN: 7526

American (AMR) AF: 0.331 AC: 3627 AN: 10952

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 1179 AN: 9844

East Asian (EAS) AF: 0.182 AC: 3421 AN: 18810

South Asian (SAS) AF: 0.145 AC: 5692 AN: 39384

European-Finnish (FIN) AF: 0.284 AC: 5713 AN: 20136

Middle Eastern (MID) AF: 0.0923 AC: 136 AN: 1474

European-Non Finnish (NFE) AF: 0.236 AC: 44271 AN: 187298

Other (OTH) AF: 0.208 AC: 3822 AN: 18376

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

African (AFR) AF: 0.0928 AC: 3838 AN: 41360

American (AMR) AF: 0.359 AC: 5467 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 636 AN: 3472

East Asian (EAS) AF: 0.270 AC: 1351 AN: 5002

South Asian (SAS) AF: 0.164 AC: 788 AN: 4792

European-Finnish (FIN) AF: 0.346 AC: 3621 AN: 10478

Middle Eastern (MID) AF: 0.147 AC: 42 AN: 286

European-Non Finnish (NFE) AF: 0.290 AC: 19711 AN: 67872

Other (OTH) AF: 0.241 AC: 507 AN: 2108

Alfa AF: 0.263 Hom.: 705

Bravo AF: 0.239

Asia WGS AF: 0.242 AC: 841 AN: 3474

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	-0.83
CADD	Benign	1.2
DANN	Benign	0.77
PhyloP100		0.057
PromoterAI		0.0016	Neutral
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: rs3758411; hg19: chr10-17271110;