Variant 16-30489160-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_002209.3(ITGAL):c.1080+5G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000937 in 1,613,982 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0050 ( 7 hom., cov: 31)

Exomes 𝑓: 0.00051 ( 7 hom. )

Consequence

ITGAL
NM_002209.3 splice_region, intron

Scores

Splicing: ADA: 1.000

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.06

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 -10 ACMG points.

BP6

Variant 16-30489160-G-A is Benign according to our data. Variant chr16-30489160-G-A is described in ClinVar as [Benign]. Clinvar id is 717785.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00504 (768/152288) while in subpopulation AFR AF= 0.0177 (736/41568). AF 95% confidence interval is 0.0166. There are 7 homozygotes in gnomad4. There are 346 alleles in male gnomad4 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.1080+5G>A		splice_region_variant, 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.1080+5G>A		splice_region_variant, intron_variant		1	NM_002209.3	ENSP00000349252.5		P20701-1

Frequencies

GnomAD3 genomes

AF:

0.00502

AC:

764

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0177

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00157

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00383

GnomAD3 exomes

AF:

0.00148

AC:

371

AN:

251402

Hom.:

AF XY:

0.00114

AC XY:

155

AN XY:

135876

show subpopulations

Gnomad AFR exome

AF:

0.0199

Gnomad AMR exome

AF:

0.00116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.000815

GnomAD4 exome

AF:

0.000509

AC:

744

AN:

1461694

Hom.:

Cov.:

AF XY:

0.000422

AC XY:

307

AN XY:

727150

show subpopulations

Gnomad4 AFR exome

AF:

0.0180

Gnomad4 AMR exome

AF:

0.00103

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000126

Gnomad4 OTH exome

AF:

0.00108

GnomAD4 genome

AF:

0.00504

AC:

768

AN:

152288

Hom.:

Cov.:

AF XY:

0.00465

AC XY:

346

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.0177

Gnomad4 AMR

AF:

0.00157

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.00200

Hom.:

Bravo

AF:

0.00584

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Mar 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Benign

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.95

SpliceAI score (max)

0.36

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.36

Position offset: -5

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