chr16-30484091-T-C

Variant names:

• chr16-30484091-T-C
• rs2285459
• NM_002209.3:c.856-22T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 35 publications found

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]

ENSG00000261346 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002209.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGAL	NM_002209.3	MANE Select	c.856-22T>C		intron	N/A	NP_002200.2	P20701-1
	ITGAL	NM_001114380.2		c.607-22T>C		intron	N/A	NP_001107852.1	P20701-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGAL	ENST00000356798.11	TSL:1 MANE Select	c.856-22T>C		intron	N/A	ENSP00000349252.5	P20701-1
	ITGAL	ENST00000358164.9	TSL:1	c.607-22T>C		intron	N/A	ENSP00000350886.5	P20701-3
	ITGAL	ENST00000955586.1		c.862-22T>C		intron	N/A	ENSP00000625645.1

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

GnomAD2 exomes AF: 0.662 AC: 164747 AN: 248854 AF XY: 0.659

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 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

African (AFR) AF: 0.662 AC: 22037 AN: 33294

American (AMR) AF: 0.776 AC: 34362 AN: 44304

Ashkenazi Jewish (ASJ) AF: 0.647 AC: 16736 AN: 25862

East Asian (EAS) AF: 0.992 AC: 39178 AN: 39496

South Asian (SAS) AF: 0.763 AC: 65418 AN: 85780

European-Finnish (FIN) AF: 0.594 AC: 31661 AN: 53296

Middle Eastern (MID) AF: 0.677 AC: 3888 AN: 5740

European-Non Finnish (NFE) AF: 0.547 AC: 605342 AN: 1106316

Other (OTH) AF: 0.618 AC: 37173 AN: 60104

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

African (AFR) AF: 0.662 AC: 27390 AN: 41404

American (AMR) AF: 0.703 AC: 10696 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.661 AC: 2294 AN: 3472

East Asian (EAS) AF: 0.989 AC: 5113 AN: 5172

South Asian (SAS) AF: 0.790 AC: 3806 AN: 4816

European-Finnish (FIN) AF: 0.587 AC: 6169 AN: 10518

Middle Eastern (MID) AF: 0.677 AC: 199 AN: 294

European-Non Finnish (NFE) AF: 0.553 AC: 37555 AN: 67960

Other (OTH) AF: 0.654 AC: 1378 AN: 2106

Alfa AF: 0.593 Hom.: 86999

Bravo AF: 0.638

Asia WGS AF: 0.876 AC: 3044 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.1
DANN	Benign	0.70
PhyloP100		-0.73
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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