rs10460526

Positions:

• chr2-36705700-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_053276.4(VIT):​c.-19+8727C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 152,096 control chromosomes in the GnomAD database, including 8,316 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.31 (8316 hom., cov: 32)
• Consequence: VIT NM_053276.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.99

Genes affected

VIT (HGNC:12697): (vitrin) This gene encodes an extracellular matrix (ECM) protein. The protein may be associated with cell adhesion and migration. High levels of expression of the protein in specific parts of the brain suggest its likely role in neural development. [provided by RefSeq, Jun 2016]

LOC124905990 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VIT	NM_053276.4	c.-19+8727C>T		intron_variant		ENST00000379242.8
LOC124905990	XR_007086283.1	n.335-16040G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VIT	ENST00000379242.8	c.-19+8727C>T		intron_variant		2	NM_053276.4	A2

Frequencies

GnomAD3 genomes AF: 0.311 AC: 47234 AN: 151978 Hom.: 8320 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.346

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.455

Gnomad EAS AF: 0.239

Gnomad SAS AF: 0.432

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.335

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.310 AC: 47219 AN: 152096 Hom.: 8316 Cov.: 32 AF XY: 0.311 AC XY: 23136 AN XY: 74316

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.320

Gnomad4 ASJ AF: 0.455

Gnomad4 EAS AF: 0.239

Gnomad4 SAS AF: 0.433

Gnomad4 FIN AF: 0.359

Gnomad4 NFE AF: 0.392

Gnomad4 OTH AF: 0.332

Alfa AF: 0.385 Hom.: 15993

Bravo AF: 0.296

Asia WGS AF: 0.327 AC: 1138 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.11
DANN	Benign	0.46

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: rs10460526; hg19: chr2-36932843;