Variant 16-30474235-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002209.3(ITGAL):c.101G>A(p.Arg34Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,456,710 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

ITGAL
NM_002209.3 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 0.166

Variant links:

Genes affected

ITGAL (HGNC:6148): (integrin subunit alpha L) ITGAL encodes the integrin alpha L chain. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain. This I-domain containing alpha integrin combines with the beta 2 chain (ITGB2) to form the integrin lymphocyte function-associated antigen-1 (LFA-1), which is expressed on all leukocytes. LFA-1 plays a central role in leukocyte intercellular adhesion through interactions with its ligands, ICAMs 1-3 (intercellular adhesion molecules 1 through 3), and also functions in lymphocyte costimulatory signaling. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ITGAL links:

ITGAL (HGNC:):

ITGAL links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.034938157).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGAL	NM_002209.3 linkuse as main transcript	c.101G>A	p.Arg34Gln	missense_variant	2/31	ENST00000356798.11	NP_002200.2	P20701-1B2RAL6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGAL	ENST00000356798.11 linkuse as main transcript	c.101G>A	p.Arg34Gln	missense_variant	2/31	1	NM_002209.3	ENSP00000349252.5		P20701-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000275

AC:

AN:

1456710

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

724384

show subpopulations

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Myoepithelial tumor

Uncertain:1

Uncertain significance, no assertion criteria provided

research

Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine

Nov 01, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.051

BayesDel_noAF

Benign

-0.31

CADD

Benign

7.0

DANN

Benign

0.92

DEOGEN2

Benign

0.044

T;.;.;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0088

LIST_S2

Benign

0.72

T;T;T;T

M_CAP

Benign

0.023

MetaRNN

Benign

0.035

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.97

N;N;.;.

PrimateAI

Benign

0.27

PROVEAN

Benign

0.36

N;N;N;N

REVEL

Benign

0.025

Sift

Benign

0.69

T;T;T;T

Sift4G

Benign

0.48

T;T;T;T

Polyphen

0.0020

B;.;.;B

Vest4

0.13

MutPred

0.44

Loss of methylation at R34 (P = 0.0112);Loss of methylation at R34 (P = 0.0112);Loss of methylation at R34 (P = 0.0112);Loss of methylation at R34 (P = 0.0112);

MVP

0.60

MPC

0.19

ClinPred

0.039

GERP RS

0.98

Varity_R

0.068

gMVP

0.064

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over