4-87802058-G-T

Variant names:

• chr4-87802058-G-T
• rs2616262
• NM_004967.4:c.-14-290G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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]

ENSG00000307815 (HGNC:58843):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004967.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IBSP	NM_004967.4	MANE Select	c.-14-290G>T		intron	N/A	NP_004958.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IBSP	ENST00000226284.7	TSL:1 MANE Select	c.-14-290G>T		intron	N/A	ENSP00000226284.5
	ENSG00000307815	ENST00000829020.1		n.286-15610C>A		intron	N/A
	ENSG00000307815	ENST00000829021.1		n.341-15610C>A		intron	N/A

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

African (AFR) AF: 0.384 AC: 15907 AN: 41426

American (AMR) AF: 0.518 AC: 7917 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.530 AC: 1837 AN: 3466

East Asian (EAS) AF: 0.571 AC: 2951 AN: 5166

South Asian (SAS) AF: 0.492 AC: 2369 AN: 4818

European-Finnish (FIN) AF: 0.506 AC: 5327 AN: 10538

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.498 AC: 33864 AN: 67970

Other (OTH) AF: 0.447 AC: 945 AN: 2114

Alfa AF: 0.488 Hom.: 47483

Bravo AF: 0.471

Asia WGS AF: 0.533 AC: 1848 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.049
DANN	Benign	0.39
PhyloP100		-1.4
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: rs2616262; hg19: chr4-88723210;