rs12318746

Variant names:

• chr12-54403647-C-A
• rs12318746
• NM_002205.5:c.1754G>T

Your query was ambiguous. Multiple possible variants found:

• chr12-54403647-C-A
• chr12-54403647-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002205.5(ITGA5):​c.1754G>T​(p.Arg585Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ITGA5 NM_002205.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.769
• Publications: 3 publications found

Genes affected

ITGA5 (HGNC:6141): (integrin subunit alpha 5) The product of this gene belongs to the integrin alpha chain family. Integrins are heterodimeric integral membrane proteins composed of an alpha subunit and a beta subunit that function in cell surface adhesion and signaling. The encoded preproprotein is proteolytically processed to generate light and heavy chains that comprise the alpha 5 subunit. This subunit associates with the beta 1 subunit to form a fibronectin receptor. This integrin may promote tumor invasion, and higher expression of this gene may be correlated with shorter survival time in lung cancer patients. Note that the integrin alpha 5 and integrin alpha V subunits are encoded by distinct genes. [provided by RefSeq, Oct 2015]

GPR84-AS1 (HGNC:56187): (GPR84, ZNF385A, ITGA5 and GTSF1 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002205.5. 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
	ITGA5	NM_002205.5	MANE Select	c.1754G>T	p.Arg585Ile	missense	Exon 17 of 30	NP_002196.4	P08648
	GPR84-AS1	NR_120486.1		n.207-3750C>A		intron	N/A
	GPR84-AS1	NR_120487.1		n.207-3750C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA5	ENST00000293379.9	TSL:1 MANE Select	c.1754G>T	p.Arg585Ile	missense	Exon 17 of 30	ENSP00000293379.4	P08648
	ITGA5	ENST00000945317.1		c.1808G>T	p.Arg603Ile	missense	Exon 17 of 30	ENSP00000615376.1
	ITGA5	ENST00000945318.1		c.1754G>T	p.Arg585Ile	missense	Exon 17 of 30	ENSP00000615377.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000158 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.085	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.29	T
Eigen	Benign	-0.073
Eigen_PC	Benign	-0.073
FATHMM_MKL	Benign	0.38	N
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.48	T
MetaSVM	Benign	-0.88	T
PhyloP100		0.77
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.10
Sift	Uncertain	0.019	D
Sift4G	Uncertain	0.054	T
Polyphen		0.57	P
Vest4		0.54
MutPred		0.30		Loss of disorder (P = 0.1092)
MVP		0.66
MPC		1.3
ClinPred		0.98	D
GERP RS		3.3
Varity_R		0.56
gMVP		0.41
Mutation Taster		=68/32	polymorphism

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: rs12318746; hg19: chr12-54797431;