16-30498669-C-T

Variant names:

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

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

ACMG classification

Our verdict: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGAL	NM_002209.3	MANE Select	c.1833-405C>T		intron	N/A	NP_002200.2
	ITGAL-AS1	NR_186415.1		n.674G>A		non_coding_transcript_exon	Exon 2 of 2
	ITGAL	NM_001114380.2		c.1584-405C>T		intron	N/A	NP_001107852.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGAL	ENST00000356798.11	TSL:1 MANE Select	c.1833-405C>T		intron	N/A	ENSP00000349252.5
	ITGAL	ENST00000358164.9	TSL:1	c.1584-405C>T		intron	N/A	ENSP00000350886.5
	ITGAL	ENST00000433423.2	TSL:2	c.154-538C>T		intron	N/A	ENSP00000409377.2

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

African (AFR) AF: 0.445 AC: 49 AN: 110

American (AMR) AF: 0.147 AC: 124 AN: 842

Ashkenazi Jewish (ASJ) AF: 0.246 AC: 33 AN: 134

East Asian (EAS) AF: 0.143 AC: 36 AN: 252

South Asian (SAS) AF: 0.494 AC: 170 AN: 344

European-Finnish (FIN) AF: 0.112 AC: 15 AN: 134

Middle Eastern (MID) AF: 0.625 AC: 5 AN: 8

European-Non Finnish (NFE) AF: 0.143 AC: 571 AN: 3982

Other (OTH) AF: 0.170 AC: 50 AN: 294

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

African (AFR) AF: 0.425 AC: 17594 AN: 41400

American (AMR) AF: 0.199 AC: 3029 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.276 AC: 957 AN: 3466

East Asian (EAS) AF: 0.139 AC: 720 AN: 5162

South Asian (SAS) AF: 0.600 AC: 2890 AN: 4818

European-Finnish (FIN) AF: 0.107 AC: 1126 AN: 10568

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.160 AC: 10887 AN: 67974

Other (OTH) AF: 0.254 AC: 535 AN: 2108

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.45
DANN	Benign	0.23
PhyloP100		-1.6
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: rs11574944; hg19: chr16-30509990;