16-30484091-T-C

Position:

• chr16-30484091-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002209.3(ITGAL):​c.856-22T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.592 in 1,606,062 control chromosomes in the GnomAD database, including 289,715 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.63 (30553 hom., cov: 30)
  • Exomes 𝑓: 0.59 (259162 hom.)
• Consequence: ITGAL NM_002209.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.726

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.966 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGAL	NM_002209.3	c.856-22T>C		intron_variant		ENST00000356798.11	NP_002200.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGAL	ENST00000356798.11	c.856-22T>C		intron_variant		1	NM_002209.3	ENSP00000349252.5

Frequencies

GnomAD3 genomes AF: 0.626 AC: 94988 AN: 151752 Hom.: 30506 Cov.: 30

Gnomad AFR AF: 0.661

Gnomad AMI AF: 0.538

Gnomad AMR AF: 0.702

Gnomad ASJ AF: 0.661

Gnomad EAS AF: 0.988

Gnomad SAS AF: 0.791

Gnomad FIN AF: 0.587

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.553

Gnomad OTH AF: 0.650

GnomAD3 exomes AF: 0.662 AC: 164747 AN: 248854 Hom.: 56870 AF XY: 0.659 AC XY: 88625 AN XY: 134522

Gnomad AFR exome AF: 0.662

Gnomad AMR exome AF: 0.786

Gnomad ASJ exome AF: 0.649

Gnomad EAS exome AF: 0.989

Gnomad SAS exome AF: 0.763

Gnomad FIN exome AF: 0.593

Gnomad NFE exome AF: 0.559

Gnomad OTH exome AF: 0.640

GnomAD4 exome AF: 0.589 AC: 855795 AN: 1454192 Hom.: 259162 Cov.: 40 AF XY: 0.593 AC XY: 428309 AN XY: 722286

Gnomad4 AFR exome AF: 0.662

Gnomad4 AMR exome AF: 0.776

Gnomad4 ASJ exome AF: 0.647

Gnomad4 EAS exome AF: 0.992

Gnomad4 SAS exome AF: 0.763

Gnomad4 FIN exome AF: 0.594

Gnomad4 NFE exome AF: 0.547

Gnomad4 OTH exome AF: 0.618

GnomAD4 genome AF: 0.626 AC: 95090 AN: 151870 Hom.: 30553 Cov.: 30 AF XY: 0.633 AC XY: 46986 AN XY: 74192

Gnomad4 AFR AF: 0.662

Gnomad4 AMR AF: 0.703

Gnomad4 ASJ AF: 0.661

Gnomad4 EAS AF: 0.989

Gnomad4 SAS AF: 0.790

Gnomad4 FIN AF: 0.587

Gnomad4 NFE AF: 0.553

Gnomad4 OTH AF: 0.654

Alfa AF: 0.587 Hom.: 55907

Bravo AF: 0.638

Asia WGS AF: 0.876 AC: 3044 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.1
DANN	Benign	0.70

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

LitVar

Other links and lift over

dbSNP: rs2285459; hg19: chr16-30495412; COSMIC: COSV63322730; COSMIC: COSV63322730;