Variant 16-30489395-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_002209.3(ITGAL):c.1213+9T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0124 in 1,613,430 control chromosomes in the GnomAD database, including 170 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0088 ( 7 hom., cov: 31)

Exomes 𝑓: 0.013 ( 163 hom. )

Consequence

ITGAL
NM_002209.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.589

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 16-30489395-T-G is Benign according to our data. Variant chr16-30489395-T-G is described in ClinVar as [Benign]. Clinvar id is 783065.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.0128 (18653/1461092) while in subpopulation NFE AF= 0.0158 (17582/1111350). AF 95% confidence interval is 0.0156. There are 163 homozygotes in gnomad4_exome. There are 9017 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGAL	NM_002209.3 linkuse as main transcript	c.1213+9T>G		intron_variant		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.1213+9T>G		intron_variant		1	NM_002209.3	ENSP00000349252.5		P20701-1

Frequencies

GnomAD3 genomes

AF:

0.00879

AC:

1338

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00268

Gnomad AMI

AF:

0.0515

Gnomad AMR

AF:

0.00216

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00621

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0156

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00855

AC:

2146

AN:

250884

Hom.:

AF XY:

0.00861

AC XY:

1168

AN XY:

135656

show subpopulations

Gnomad AFR exome

AF:

0.00248

Gnomad AMR exome

AF:

0.00301

Gnomad ASJ exome

AF:

0.00288

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00486

Gnomad NFE exome

AF:

0.0159

Gnomad OTH exome

AF:

0.00949

GnomAD4 exome

AF:

0.0128

AC:

18653

AN:

1461092

Hom.:

163

Cov.:

AF XY:

0.0124

AC XY:

9017

AN XY:

726748

show subpopulations

Gnomad4 AFR exome

AF:

0.00203

Gnomad4 AMR exome

AF:

0.00266

Gnomad4 ASJ exome

AF:

0.00337

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000928

Gnomad4 FIN exome

AF:

0.00498

Gnomad4 NFE exome

AF:

0.0158

Gnomad4 OTH exome

AF:

0.00838

GnomAD4 genome

AF:

0.00878

AC:

1338

AN:

152338

Hom.:

Cov.:

AF XY:

0.00816

AC XY:

608

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.00267

Gnomad4 AMR

AF:

0.00216

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00621

Gnomad4 NFE

AF:

0.0156

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.0129

Hom.:

Bravo

AF:

0.00861

Asia WGS

AF:

0.000866

AC:

AN:

3478

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	Labcorp Genetics (formerly Invitae), Labcorp	Jul 31, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

8.6

DANN

Benign

0.89

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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