rs1064524

Positions:

• chr16-30481502-C-T

Variant summary

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

The ENST00000356798.11(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. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.032 (119 hom., cov: 32)
  • Exomes 𝑓: 0.044 (1679 hom.)
• Consequence: ITGAL ENST00000356798.11 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.80

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGAL	NM_002209.3	c.640C>T	p.Arg214Trp	missense_variant	7/31	ENST00000356798.11	NP_002200.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGAL	ENST00000356798.11	c.640C>T	p.Arg214Trp	missense_variant	7/31	1	NM_002209.3	ENSP00000349252	P1
	ENST00000569459.1	n.296-2052G>A		intron_variant, non_coding_transcript_variant		3

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

GnomAD3 exomes AF: 0.0332 AC: 8345 AN: 251038 Hom.: 205 AF XY: 0.0332 AC XY: 4501 AN XY: 135672

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 SAS exome AF: 0.00800

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

Gnomad4 AFR exome AF: 0.00669

Gnomad4 AMR exome AF: 0.0159

Gnomad4 ASJ exome AF: 0.0163

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.00847

Gnomad4 FIN exome AF: 0.0591

Gnomad4 NFE exome AF: 0.0510

Gnomad4 OTH exome AF: 0.0392

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

Gnomad4 AFR AF: 0.00865

Gnomad4 AMR AF: 0.0257

Gnomad4 ASJ AF: 0.0159

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0106

Gnomad4 FIN AF: 0.0582

Gnomad4 NFE AF: 0.0484

Gnomad4 OTH AF: 0.0251

Alfa AF: 0.0426 Hom.: 370

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 v4.3

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;T;T
MetaRNN	Benign	0.0028	T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.51	N;.;.
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-2.3	N;N;N
REVEL	Benign	0.23
Sift	Benign	0.030	D;D;D
Sift4G	Uncertain	0.018	D;D;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

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: rs1064524; hg19: chr16-30492823;