16-30498669-C-T

Variant names:

• chr16-30498669-C-T
• rs11574944
• NM_002209.3:c.1833-405C>T

Variant summary

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

The NM_002209.3(ITGAL):​c.1833-405C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 158,050 control chromosomes in the GnomAD database, including 6,308 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 0.25 (6185 hom., cov: 31)
  • Exomes 𝑓: 0.17 (123 hom.)
• Consequence: ITGAL NM_002209.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.65

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-AS1 (HGNC:56737): (ITGAL antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGAL	NM_002209.3	c.1833-405C>T		intron_variant	Intron 15 of 30	ENST00000356798.11	NP_002200.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGAL	ENST00000356798.11	c.1833-405C>T		intron_variant	Intron 15 of 30	1	NM_002209.3	ENSP00000349252.5

Frequencies

GnomAD3 genomes AF: 0.250 AC: 38020 AN: 151832 Hom.: 6177 Cov.: 31

Gnomad AFR AF: 0.425

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.601

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.248

GnomAD4 exome AF: 0.173 AC: 1053 AN: 6100 Hom.: 123 AF XY: 0.181 AC XY: 572 AN XY: 3154

Gnomad4 AFR exome AF: 0.445

Gnomad4 AMR exome AF: 0.147

Gnomad4 ASJ exome AF: 0.246

Gnomad4 EAS exome AF: 0.143

Gnomad4 SAS exome AF: 0.494

Gnomad4 FIN exome AF: 0.112

Gnomad4 NFE exome AF: 0.143

Gnomad4 OTH exome AF: 0.170

GnomAD4 genome AF: 0.250 AC: 38049 AN: 151950 Hom.: 6185 Cov.: 31 AF XY: 0.255 AC XY: 18921 AN XY: 74276

Gnomad4 AFR AF: 0.425

Gnomad4 AMR AF: 0.199

Gnomad4 ASJ AF: 0.276

Gnomad4 EAS AF: 0.139

Gnomad4 SAS AF: 0.600

Gnomad4 FIN AF: 0.107

Gnomad4 NFE AF: 0.160

Gnomad4 OTH AF: 0.254

Alfa AF: 0.191 Hom.: 452

Bravo AF: 0.252

Asia WGS AF: 0.421 AC: 1461 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.45
DANN	Benign	0.23

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: rs11574944; hg19: chr16-30509990;