rs2230433

Variant names:

• chr16-30506720-G-C
• rs2230433
• NM_002209.3:c.2372G>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.2372G>C​(p.Arg791Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 1,611,008 control chromosomes in the GnomAD database, including 86,195 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.33 (8963 hom., cov: 30)
  • Exomes 𝑓: 0.31 (77232 hom.)
• Consequence: ITGAL NM_002209.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14
• Publications: 56 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 (MetaRNN=4.544136E-6).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.637 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGAL	NM_002209.3	c.2372G>C	p.Arg791Thr	missense_variant	Exon 21 of 31	ENST00000356798.11	NP_002200.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGAL	ENST00000356798.11	c.2372G>C	p.Arg791Thr	missense_variant	Exon 21 of 31	1	NM_002209.3	ENSP00000349252.5

Frequencies

GnomAD3 genomes AF: 0.329 AC: 49857 AN: 151500 Hom.: 8948 Cov.: 30

Gnomad AFR AF: 0.422

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.314

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.656

Gnomad FIN AF: 0.254

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.299

GnomAD2 exomes AF: 0.312 AC: 78172 AN: 250674 AF XY: 0.332

Gnomad AFR exome AF: 0.422

Gnomad AMR exome AF: 0.182

Gnomad ASJ exome AF: 0.301

Gnomad EAS exome AF: 0.130

Gnomad FIN exome AF: 0.250

Gnomad NFE exome AF: 0.284

Gnomad OTH exome AF: 0.296

GnomAD4 exome AF: 0.309 AC: 450521 AN: 1459390 Hom.: 77232 Cov.: 33 AF XY: 0.319 AC XY: 231993 AN XY: 726156

African (AFR) AF: 0.420 AC: 14031 AN: 33438

American (AMR) AF: 0.190 AC: 8497 AN: 44640

Ashkenazi Jewish (ASJ) AF: 0.307 AC: 8014 AN: 26098

East Asian (EAS) AF: 0.134 AC: 5315 AN: 39658

South Asian (SAS) AF: 0.652 AC: 56178 AN: 86188

European-Finnish (FIN) AF: 0.253 AC: 13496 AN: 53354

Middle Eastern (MID) AF: 0.300 AC: 1730 AN: 5760

European-Non Finnish (NFE) AF: 0.292 AC: 323638 AN: 1109960

Other (OTH) AF: 0.325 AC: 19622 AN: 60294

GnomAD4 genome AF: 0.329 AC: 49911 AN: 151618 Hom.: 8963 Cov.: 30 AF XY: 0.334 AC XY: 24700 AN XY: 74056

African (AFR) AF: 0.422 AC: 17414 AN: 41308

American (AMR) AF: 0.257 AC: 3904 AN: 15194

Ashkenazi Jewish (ASJ) AF: 0.314 AC: 1090 AN: 3472

East Asian (EAS) AF: 0.142 AC: 734 AN: 5154

South Asian (SAS) AF: 0.656 AC: 3136 AN: 4782

European-Finnish (FIN) AF: 0.254 AC: 2665 AN: 10480

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.294 AC: 19951 AN: 67928

Other (OTH) AF: 0.304 AC: 640 AN: 2106

Alfa AF: 0.294 Hom.: 5146

Bravo AF: 0.318

TwinsUK AF: 0.295 AC: 1094

ALSPAC AF: 0.291 AC: 1122

ESP6500AA AF: 0.416 AC: 1827

ESP6500EA AF: 0.290 AC: 2498

ExAC AF: 0.325 AC: 39468

Asia WGS AF: 0.443 AC: 1544 AN: 3478

EpiCase AF: 0.293

EpiControl AF: 0.288

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	7.9
DANN	Benign	0.93
DEOGEN2	Benign	0.065	T;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.61	T;T
MetaRNN	Benign	0.0000045	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N;.
PhyloP100		-1.1
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.8	N;N
REVEL	Benign	0.030
Sift	Benign	0.25	T;T
Sift4G	Benign	0.26	T;T
Polyphen		0.0	B;.
Vest4		0.053
MPC		0.45
ClinPred		0.021	T
GERP RS		-10
Varity_R		0.10
gMVP		0.62
Mutation Taster		=96/4	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs2230433; hg19: chr16-30518041; COSMIC: COSV63319945; COSMIC: COSV63319945;