17-3720391-A-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002208.5(ITGAE):c.3249T>A(p.Asp1083Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000148 in 1,483,396 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

ITGAE
NM_002208.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0450

Publications

0 publications found

Variant links:

COSMIC-nc: COSV54000811

Genes affected

ITGAE (HGNC:6147): (integrin subunit alpha E) Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain. This gene encodes an I-domain-containing alpha integrin that undergoes post-translational cleavage in the extracellular domain, yielding disulfide-linked heavy and light chains. In combination with the beta 7 integrin, this protein forms the E-cadherin binding integrin known as the human mucosal lymphocyte-1 antigen. This protein is preferentially expressed in human intestinal intraepithelial lymphocytes (IEL), and in addition to a role in adhesion, it may serve as an accessory molecule for IEL activation. [provided by RefSeq, Jul 2008]

ITGAE links:

P2RX5 (HGNC:8536): (purinergic receptor P2X 5) The product of this gene belongs to the family of purinoceptors for ATP. This receptor functions as a ligand-gated ion channel. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the neighboring downstream gene, TAX1BP3 (Tax1 binding protein 3). [provided by RefSeq, Mar 2011]

P2RX5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10172334).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002208.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ITGAE	NM_002208.5	MANE Select	c.3249T>A	p.Asp1083Glu	missense	Exon 29 of 31	NP_002199.3
ITGAE	NM_001425071.1		c.3171T>A	p.Asp1057Glu	missense	Exon 28 of 30	NP_001412000.1
ITGAE	NM_001425072.1		c.3096T>A	p.Asp1032Glu	missense	Exon 27 of 29	NP_001412001.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ITGAE	ENST00000263087.9	TSL:1 MANE Select	c.3249T>A	p.Asp1083Glu	missense	Exon 29 of 31	ENSP00000263087.4	P38570
ITGAE	ENST00000572179.5	TSL:1	n.162T>A		non_coding_transcript_exon	Exon 2 of 4
ITGAE	ENST00000949198.1		c.3345T>A	p.Asp1115Glu	missense	Exon 29 of 31	ENSP00000619257.1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000239

AC:

AN:

250712

AF XY:

0.0000295

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000272

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000150

AC:

AN:

1331084

Hom.:

Cov.:

AF XY:

0.0000105

AC XY:

AN XY:

669164

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30806

American (AMR)

AF:

0.00

AC:

AN:

44484

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25326

East Asian (EAS)

AF:

0.000128

AC:

AN:

39072

South Asian (SAS)

AF:

0.0000239

AC:

AN:

83558

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53346

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5512

European-Non Finnish (NFE)

AF:

0.0000131

AC:

AN:

993006

Other (OTH)

AF:

0.00

AC:

AN:

55974

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152312

Hom.:

Cov.:

AF XY:

0.0000268

AC XY:

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41566

American (AMR)

AF:

0.00

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000386

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000247

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.060

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.026

LIST_S2

Benign

0.36

M_CAP

Benign

0.0056

MetaRNN

Benign

0.10

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.4

PhyloP100

0.045

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.91

REVEL

Benign

0.11

Sift

Benign

0.14

Sift4G

Benign

0.076

Polyphen

0.86

Vest4

0.10

MutPred

0.52

Gain of ubiquitination at K1082 (P = 0.0985)

MVP

0.57

MPC

0.16

ClinPred

0.088

GERP RS

1.3

Varity_R

0.029

gMVP

0.17

Mutation Taster

=95/5

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over