Variant 12-54401626-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002205.5(ITGA5):c.2346T>C(p.Phe782Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0192 in 1,614,046 control chromosomes in the GnomAD database, including 1,018 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.043 ( 327 hom., cov: 32)

Exomes 𝑓: 0.017 ( 691 hom. )

Consequence

ITGA5
NM_002205.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.17

Variant links:

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]

ITGA5 links:

ITGA5 (HGNC:):

ITGA5 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 12-54401626-A-G is Benign according to our data. Variant chr12-54401626-A-G is described in ClinVar as [Benign]. Clinvar id is 1243290.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=3.17 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGA5	NM_002205.5 linkuse as main transcript	c.2346T>C	p.Phe782Phe	synonymous_variant	23/30	ENST00000293379.9	NP_002196.4	P08648B2R627
ITGA5	XM_024448970.2 linkuse as main transcript	c.834T>C	p.Phe278Phe	synonymous_variant	10/17		XP_024304738.1
GPR84-AS1	NR_120486.1 linkuse as main transcript	n.207-5771A>G		intron_variant
GPR84-AS1	NR_120487.1 linkuse as main transcript	n.207-5771A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGA5	ENST00000293379.9 linkuse as main transcript	c.2346T>C	p.Phe782Phe	synonymous_variant	23/30	1	NM_002205.5	ENSP00000293379.4		P08648

Frequencies

GnomAD3 genomes

AF:

0.0427

AC:

6494

AN:

152054

Hom.:

321

Cov.:

show subpopulations

Gnomad AFR

AF:

0.117

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0171

Gnomad ASJ

AF:

0.0225

Gnomad EAS

AF:

0.00501

Gnomad SAS

AF:

0.0881

Gnomad FIN

AF:

0.0144

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00960

Gnomad OTH

AF:

0.0263

GnomAD3 exomes

AF:

0.0256

AC:

6434

AN:

251434

Hom.:

239

AF XY:

0.0264

AC XY:

3593

AN XY:

135890

show subpopulations

Gnomad AFR exome

AF:

0.118

Gnomad AMR exome

AF:

0.00755

Gnomad ASJ exome

AF:

0.0178

Gnomad EAS exome

AF:

0.00424

Gnomad SAS exome

AF:

0.0786

Gnomad FIN exome

AF:

0.0147

Gnomad NFE exome

AF:

0.0101

Gnomad OTH exome

AF:

0.0199

GnomAD4 exome

AF:

0.0168

AC:

24527

AN:

1461874

Hom.:

691

Cov.:

AF XY:

0.0182

AC XY:

13241

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.125

Gnomad4 AMR exome

AF:

0.00879

Gnomad4 ASJ exome

AF:

0.0202

Gnomad4 EAS exome

AF:

0.00640

Gnomad4 SAS exome

AF:

0.0757

Gnomad4 FIN exome

AF:

0.0140

Gnomad4 NFE exome

AF:

0.00942

Gnomad4 OTH exome

AF:

0.0220

GnomAD4 genome

AF:

0.0428

AC:

6515

AN:

152172

Hom.:

327

Cov.:

AF XY:

0.0425

AC XY:

3162

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.117

Gnomad4 AMR

AF:

0.0171

Gnomad4 ASJ

AF:

0.0225

Gnomad4 EAS

AF:

0.00502

Gnomad4 SAS

AF:

0.0878

Gnomad4 FIN

AF:

0.0144

Gnomad4 NFE

AF:

0.00959

Gnomad4 OTH

AF:

0.0293

Alfa

AF:

0.0254

Hom.:

Bravo

AF:

0.0448

Asia WGS

AF:

0.0660

AC:

234

AN:

3478

EpiCase

AF:

0.00862

EpiControl

AF:

0.00948

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.86

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over