3-124856796-C-G

Position:

• chr3-124856796-C-G

Variant summary

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

The NM_002213.5(ITGB5):​c.361+2446G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 151,992 control chromosomes in the GnomAD database, including 15,174 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 0.44 (15174 hom., cov: 32)
• Consequence: ITGB5 NM_002213.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0430

Genes affected

ITGB5 (HGNC:6160): (integrin subunit beta 5) This gene encodes a beta subunit of integrin, which can combine with different alpha chains to form a variety of integrin heterodimers. Integrins are integral cell-surface receptors that participate in cell adhesion as well as cell-surface mediated signaling. The alphav beta5 integrin is involved in adhesion to vitronectin. [provided by RefSeq, Aug 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.651 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGB5	NM_002213.5	c.361+2446G>C		intron_variant		ENST00000296181.9	NP_002204.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGB5	ENST00000296181.9	c.361+2446G>C		intron_variant		1	NM_002213.5	ENSP00000296181	P1

Frequencies

GnomAD3 genomes AF: 0.443 AC: 67292 AN: 151874 Hom.: 15167 Cov.: 32

Gnomad AFR AF: 0.482

Gnomad AMI AF: 0.397

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.497

Gnomad EAS AF: 0.671

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.417

Gnomad OTH AF: 0.447

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

GnomAD4 genome AF: 0.443 AC: 67329 AN: 151992 Hom.: 15174 Cov.: 32 AF XY: 0.443 AC XY: 32929 AN XY: 74302

Gnomad4 AFR AF: 0.482

Gnomad4 AMR AF: 0.393

Gnomad4 ASJ AF: 0.497

Gnomad4 EAS AF: 0.670

Gnomad4 SAS AF: 0.389

Gnomad4 FIN AF: 0.428

Gnomad4 NFE AF: 0.417

Gnomad4 OTH AF: 0.448

Alfa AF: 0.328 Hom.: 895

Bravo AF: 0.445

Asia WGS AF: 0.500 AC: 1740 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.5
DANN	Benign	0.52

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: rs1499961; hg19: chr3-124575643;