16-30481502-C-T

Variant names:

• chr16-30481502-C-T
• rs1064524
• NM_002209.3:c.640C>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.640C>T​(p.Arg214Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0429 in 1,612,466 control chromosomes in the GnomAD database, including 1,798 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 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 0.032 (119 hom., cov: 32)
  • Exomes 𝑓: 0.044 (1679 hom.)
• Consequence: ITGAL NM_002209.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.80
• Publications: 32 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 (MetaRNN=0.0028294325).
• BA1: GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0507 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.640C>T	p.Arg214Trp	missense	Exon 7 of 31	NP_002200.2	P20701-1
	ITGAL	NM_001114380.2		c.391C>T	p.Arg131Trp	missense	Exon 5 of 29	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.640C>T	p.Arg214Trp	missense	Exon 7 of 31	ENSP00000349252.5	P20701-1
	ITGAL	ENST00000358164.9	TSL:1	c.391C>T	p.Arg131Trp	missense	Exon 5 of 29	ENSP00000350886.5	P20701-3
	ITGAL	ENST00000955586.1		c.646C>T	p.Arg216Trp	missense	Exon 7 of 31	ENSP00000625645.1

Frequencies

GnomAD3 genomes AF: 0.0322 AC: 4900 AN: 152000 Hom.: 119 Cov.: 32

Gnomad AFR AF: 0.00867

Gnomad AMI AF: 0.0892

Gnomad AMR AF: 0.0257

Gnomad ASJ AF: 0.0159

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0104

Gnomad FIN AF: 0.0582

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0484

Gnomad OTH AF: 0.0253

GnomAD2 exomes AF: 0.0332 AC: 8345 AN: 251038 AF XY: 0.0332

Gnomad AFR exome AF: 0.00800

Gnomad AMR exome AF: 0.0151

Gnomad ASJ exome AF: 0.0167

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.0587

Gnomad NFE exome AF: 0.0510

Gnomad OTH exome AF: 0.0346

GnomAD4 exome AF: 0.0441 AC: 64356 AN: 1460348 Hom.: 1679 Cov.: 31 AF XY: 0.0431 AC XY: 31334 AN XY: 726492

African (AFR) AF: 0.00669 AC: 224 AN: 33458

American (AMR) AF: 0.0159 AC: 711 AN: 44642

Ashkenazi Jewish (ASJ) AF: 0.0163 AC: 427 AN: 26122

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39698

South Asian (SAS) AF: 0.00847 AC: 730 AN: 86136

European-Finnish (FIN) AF: 0.0591 AC: 3154 AN: 53410

Middle Eastern (MID) AF: 0.0127 AC: 73 AN: 5764

European-Non Finnish (NFE) AF: 0.0510 AC: 56668 AN: 1110786

Other (OTH) AF: 0.0392 AC: 2365 AN: 60332

GnomAD4 genome AF: 0.0322 AC: 4898 AN: 152118 Hom.: 119 Cov.: 32 AF XY: 0.0326 AC XY: 2421 AN XY: 74352

African (AFR) AF: 0.00865 AC: 359 AN: 41524

American (AMR) AF: 0.0257 AC: 392 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.0159 AC: 55 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.0106 AC: 51 AN: 4824

European-Finnish (FIN) AF: 0.0582 AC: 615 AN: 10572

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0484 AC: 3287 AN: 67980

Other (OTH) AF: 0.0251 AC: 53 AN: 2114

Alfa AF: 0.0417 Hom.: 664

Bravo AF: 0.0297

TwinsUK AF: 0.0526 AC: 195

ALSPAC AF: 0.0547 AC: 211

ESP6500AA AF: 0.0123 AC: 54

ESP6500EA AF: 0.0490 AC: 421

ExAC AF: 0.0352 AC: 4277

Asia WGS AF: 0.00751 AC: 27 AN: 3478

EpiCase AF: 0.0439

EpiControl AF: 0.0438

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	3.5
DANN	Benign	0.80
DEOGEN2	Uncertain	0.59	D
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.032	N
LIST_S2	Benign	0.48	T
MetaRNN	Benign	0.0028	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.51	N
PhyloP100		-3.8
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.23
Sift	Benign	0.030	D
Sift4G	Uncertain	0.018	D
Polyphen		0.0020	B
Vest4		0.044
MPC		0.90
ClinPred		0.012	T
GERP RS		-8.2
Varity_R		0.34
gMVP		0.69
Mutation Taster		=97/3	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: rs1064524; hg19: chr16-30492823; COSMIC: COSV107441787; COSMIC: COSV107441787;