16-30503402-C-T

Variant names:

• chr16-30503402-C-T
• rs4243232
• NM_002209.3:c.2146-773C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002209.3(ITGAL):​c.2146-773C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.613 in 151,204 control chromosomes in the GnomAD database, including 29,543 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 0.61 (29543 hom., cov: 28)
• Consequence: ITGAL NM_002209.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.255
• Publications: 12 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• 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.2146-773C>T		intron	N/A	NP_002200.2	P20701-1
	ITGAL	NM_001114380.2		c.1897-773C>T		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.2146-773C>T		intron	N/A	ENSP00000349252.5	P20701-1
	ITGAL	ENST00000358164.9	TSL:1	c.1897-773C>T		intron	N/A	ENSP00000350886.5	P20701-3
	ITGAL	ENST00000955586.1		c.2152-773C>T		intron	N/A	ENSP00000625645.1

Frequencies

GnomAD3 genomes AF: 0.613 AC: 92645 AN: 151100 Hom.: 29499 Cov.: 28

Gnomad AFR AF: 0.686

Gnomad AMI AF: 0.537

Gnomad AMR AF: 0.713

Gnomad ASJ AF: 0.636

Gnomad EAS AF: 0.989

Gnomad SAS AF: 0.769

Gnomad FIN AF: 0.565

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.513

Gnomad OTH AF: 0.637

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.613 AC: 92743 AN: 151204 Hom.: 29543 Cov.: 28 AF XY: 0.622 AC XY: 45905 AN XY: 73792

African (AFR) AF: 0.686 AC: 28260 AN: 41174

American (AMR) AF: 0.713 AC: 10768 AN: 15092

Ashkenazi Jewish (ASJ) AF: 0.636 AC: 2206 AN: 3470

East Asian (EAS) AF: 0.989 AC: 5111 AN: 5168

South Asian (SAS) AF: 0.768 AC: 3688 AN: 4800

European-Finnish (FIN) AF: 0.565 AC: 5827 AN: 10312

Middle Eastern (MID) AF: 0.653 AC: 192 AN: 294

European-Non Finnish (NFE) AF: 0.513 AC: 34849 AN: 67878

Other (OTH) AF: 0.642 AC: 1353 AN: 2106

Alfa AF: 0.573 Hom.: 17435

Bravo AF: 0.629

Asia WGS AF: 0.866 AC: 3009 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.9
DANN	Benign	0.61
PhyloP100		-0.26
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: rs4243232; hg19: chr16-30514723;