chr3-124773748-C-T

Variant names:

• chr3-124773748-C-T
• rs1243298041
• NM_002213.5:c.1858G>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002213.5(ITGB5):​c.1858G>A​(p.Ala620Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,492 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ITGB5 NM_002213.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.56

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGB5	NM_002213.5	c.1858G>A	p.Ala620Thr	missense_variant	Exon 11 of 15	ENST00000296181.9	NP_002204.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGB5	ENST00000296181.9	c.1858G>A	p.Ala620Thr	missense_variant	Exon 11 of 15	1	NM_002213.5	ENSP00000296181.4
ITGB5	ENST00000481591.5	c.925G>A	p.Ala309Thr	missense_variant	Exon 5 of 7	5		ENSP00000420814.1
ITGB5	ENST00000461306.1	n.197G>A		non_coding_transcript_exon_variant	Exon 2 of 5	4
ITGB5	ENST00000488466.5	c.*71G>A		downstream_gene_variant		5		ENSP00000477446.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251348 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135870

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460492 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 726576

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 23, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1858G>A (p.A620T) alteration is located in exon 11 (coding exon 11) of the ITGB5 gene. This alteration results from a G to A substitution at nucleotide position 1858, causing the alanine (A) at amino acid position 620 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Uncertain	0.021	T
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.34	T
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.039	D
MetaRNN	Uncertain	0.56	D
MetaSVM	Uncertain	0.17	D
MutationAssessor	Benign	0.24	N
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.9	N
REVEL	Uncertain	0.40
Sift	Benign	0.094	T
Sift4G	Benign	0.38	T
Polyphen		0.76	P
Vest4		0.56
MutPred		0.49		Loss of catalytic residue at A620 (P = 0.0396);
MVP		0.97
MPC		0.53
ClinPred		0.55	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.10
gMVP		0.73

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: rs1243298041; hg19: chr3-124492595;