10-17229207-G-C

Position:

• chr10-17229207-G-C

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.-147-69G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.035 in 353,666 control chromosomes in the GnomAD database, including 211 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.024 (56 hom., cov: 31)
  • Exomes 𝑓: 0.043 (155 hom.)
• Consequence: VIM NM_003380.5 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.800

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 10-17229207-G-C is Benign according to our data. Variant chr10-17229207-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1316913.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VIM	NM_003380.5	c.-147-69G>C		intron_variant		ENST00000544301.7	NP_003371.2
VIM-AS1	NR_108061.1	n.641+138C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VIM	ENST00000544301.7	c.-147-69G>C		intron_variant		1	NM_003380.5	ENSP00000446007	P1
VIM-AS1	ENST00000605833.2	n.674+138C>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0236 AC: 3376 AN: 143280 Hom.: 56 Cov.: 31

Gnomad AFR AF: 0.0134

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0244

Gnomad ASJ AF: 0.0189

Gnomad EAS AF: 0.000905

Gnomad SAS AF: 0.00692

Gnomad FIN AF: 0.0535

Gnomad MID AF: 0.0445

Gnomad NFE AF: 0.0282

Gnomad OTH AF: 0.0255

GnomAD4 exome AF: 0.0427 AC: 8989 AN: 210322 Hom.: 155 Cov.: 4 AF XY: 0.0398 AC XY: 4567 AN XY: 114686

Gnomad4 AFR exome AF: 0.0524

Gnomad4 AMR exome AF: 0.0335

Gnomad4 ASJ exome AF: 0.0464

Gnomad4 EAS exome AF: 0.000138

Gnomad4 SAS exome AF: 0.00734

Gnomad4 FIN exome AF: 0.0762

Gnomad4 NFE exome AF: 0.0519

Gnomad4 OTH exome AF: 0.0503

GnomAD4 genome AF: 0.0235 AC: 3375 AN: 143344 Hom.: 56 Cov.: 31 AF XY: 0.0242 AC XY: 1679 AN XY: 69346

Gnomad4 AFR AF: 0.0135

Gnomad4 AMR AF: 0.0244

Gnomad4 ASJ AF: 0.0189

Gnomad4 EAS AF: 0.000908

Gnomad4 SAS AF: 0.00670

Gnomad4 FIN AF: 0.0535

Gnomad4 NFE AF: 0.0282

Gnomad4 OTH AF: 0.0253

Alfa AF: 0.00965 Hom.: 0

Bravo AF: 0.0204

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 29, 2019	- -
Likely 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	-0.68
CADD	Benign	14
DANN	Benign	0.88
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs55877356; hg19: chr10-17271206;