3-124856796-C-G

Variant names:

• chr3-124856796-C-G
• rs1499961
• NM_002213.5:c.361+2446G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002213.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB5	NM_002213.5	MANE Select	c.361+2446G>C		intron	N/A	NP_002204.2
	ITGB5	NM_001354764.2		c.37+2446G>C		intron	N/A	NP_001341693.1
	ITGB5	NM_001354765.1		c.37+2446G>C		intron	N/A	NP_001341694.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB5	ENST00000296181.9	TSL:1 MANE Select	c.361+2446G>C		intron	N/A	ENSP00000296181.4	P18084
	ITGB5	ENST00000905025.1		c.361+2446G>C		intron	N/A	ENSP00000575084.1
	ITGB5	ENST00000965613.1		c.361+2446G>C		intron	N/A	ENSP00000635672.1

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

African (AFR) AF: 0.482 AC: 19965 AN: 41436

American (AMR) AF: 0.393 AC: 6003 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.497 AC: 1724 AN: 3468

East Asian (EAS) AF: 0.670 AC: 3463 AN: 5168

South Asian (SAS) AF: 0.389 AC: 1872 AN: 4816

European-Finnish (FIN) AF: 0.428 AC: 4512 AN: 10548

Middle Eastern (MID) AF: 0.497 AC: 145 AN: 292

European-Non Finnish (NFE) AF: 0.417 AC: 28341 AN: 67962

Other (OTH) AF: 0.448 AC: 943 AN: 2106

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.5
DANN	Benign	0.52
PhyloP100		0.043
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: rs1499961; hg19: chr3-124575643;