4-87802058-G-T

Position:

• chr4-87802058-G-T

Variant summary

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

The NM_004967.4(IBSP):​c.-14-290G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.473 in 151,974 control chromosomes in the GnomAD database, including 17,393 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 0.47 (17393 hom., cov: 32)
• Consequence: IBSP NM_004967.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.37

Genes affected

IBSP (HGNC:5341): (integrin binding sialoprotein) The protein encoded by this gene is a major structural protein of the bone matrix. It constitutes approximately 12% of the noncollagenous proteins in human bone and is synthesized by skeletal-associated cell types, including hypertrophic chondrocytes, osteoblasts, osteocytes, and osteoclasts. The only extraskeletal site of its synthesis is the trophoblast. This protein binds to calcium and hydroxyapatite via its acidic amino acid clusters, and mediates cell attachment through an RGD sequence that recognizes the vitronectin receptor. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IBSP	NM_004967.4	c.-14-290G>T		intron_variant		ENST00000226284.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IBSP	ENST00000226284.7	c.-14-290G>T		intron_variant		1	NM_004967.4	P1

Frequencies

GnomAD3 genomes AF: 0.473 AC: 71808 AN: 151856 Hom.: 17390 Cov.: 32

Gnomad AFR AF: 0.384

Gnomad AMI AF: 0.675

Gnomad AMR AF: 0.518

Gnomad ASJ AF: 0.530

Gnomad EAS AF: 0.572

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.506

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.498

Gnomad OTH AF: 0.447

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

GnomAD4 genome AF: 0.473 AC: 71835 AN: 151974 Hom.: 17393 Cov.: 32 AF XY: 0.474 AC XY: 35229 AN XY: 74272

Gnomad4 AFR AF: 0.384

Gnomad4 AMR AF: 0.518

Gnomad4 ASJ AF: 0.530

Gnomad4 EAS AF: 0.571

Gnomad4 SAS AF: 0.492

Gnomad4 FIN AF: 0.506

Gnomad4 NFE AF: 0.498

Gnomad4 OTH AF: 0.447

Alfa AF: 0.486 Hom.: 17829

Bravo AF: 0.471

Asia WGS AF: 0.533 AC: 1848 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.049
DANN	Benign	0.39

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: rs2616262; hg19: chr4-88723210;