10-17228992-C-T

Position:

• chr10-17228992-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_003380.5(VIM):​c.-147-284C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00975 in 243,040 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0098 (15 hom., cov: 33)
  • Exomes 𝑓: 0.0096 (14 hom.)
• Consequence: VIM NM_003380.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.776

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=-0.93).
• BP6: Variant 10-17228992-C-T is Benign according to our data. Variant chr10-17228992-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1316887.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00985 (1500/152288) while in subpopulation AMR AF= 0.0174 (267/15302). AF 95% confidence interval is 0.0157. There are 15 homozygotes in gnomad4. There are 723 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1500 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VIM	NM_003380.5	c.-147-284C>T		intron_variant		ENST00000544301.7
VIM-AS1	NR_108061.1	n.641+353G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VIM	ENST00000544301.7	c.-147-284C>T		intron_variant		1	NM_003380.5	P1
VIM-AS1	ENST00000605833.2	n.674+353G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.00986 AC: 1500 AN: 152170 Hom.: 15 Cov.: 33

Gnomad AFR AF: 0.00338

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.0175

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00558

Gnomad FIN AF: 0.00809

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0136

Gnomad OTH AF: 0.00621

GnomAD4 exome AF: 0.00959 AC: 870 AN: 90752 Hom.: 14 Cov.: 0 AF XY: 0.00972 AC XY: 474 AN XY: 48776

Gnomad4 AFR exome AF: 0.00242

Gnomad4 AMR exome AF: 0.0216

Gnomad4 ASJ exome AF: 0.00330

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00821

Gnomad4 FIN exome AF: 0.00889

Gnomad4 NFE exome AF: 0.0106

Gnomad4 OTH exome AF: 0.00615

GnomAD4 genome AF: 0.00985 AC: 1500 AN: 152288 Hom.: 15 Cov.: 33 AF XY: 0.00971 AC XY: 723 AN XY: 74464

Gnomad4 AFR AF: 0.00337

Gnomad4 AMR AF: 0.0174

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00559

Gnomad4 FIN AF: 0.00809

Gnomad4 NFE AF: 0.0136

Gnomad4 OTH AF: 0.00614

Alfa AF: 0.0116 Hom.: 0

Bravo AF: 0.0109

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 05, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.46
DANN	Benign	0.89

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: rs144610656; hg19: chr10-17270991;