16-30499341-G-C

Variant names:

• chr16-30499341-G-C
• rs200068830
• NM_002209.3:c.1997G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002209.3(ITGAL):​c.1997G>C​(p.Arg666Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. R666H) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ITGAL NM_002209.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.25
• Publications: 2 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.055210292).

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.1997G>C	p.Arg666Pro	missense	Exon 17 of 31	NP_002200.2	P20701-1
	ITGAL	NM_001114380.2		c.1748G>C	p.Arg583Pro	missense	Exon 15 of 29	NP_001107852.1	P20701-3
	ITGAL-AS1	NR_186415.1		n.191+23C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGAL	ENST00000356798.11	TSL:1 MANE Select	c.1997G>C	p.Arg666Pro	missense	Exon 17 of 31	ENSP00000349252.5	P20701-1
	ITGAL	ENST00000358164.9	TSL:1	c.1748G>C	p.Arg583Pro	missense	Exon 15 of 29	ENSP00000350886.5	P20701-3
	ITGAL	ENST00000955586.1		c.2003G>C	p.Arg668Pro	missense	Exon 17 of 31	ENSP00000625645.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.0030
DANN	Benign	0.64
DEOGEN2	Benign	0.041	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.0024	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.055	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.010	N
PhyloP100		-4.3
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.63	N
REVEL	Benign	0.050
Sift	Benign	0.22	T
Sift4G	Benign	0.17	T
Polyphen		0.0	B
Vest4		0.10
MutPred		0.63		Loss of MoRF binding (P = 0.0694)
MVP		0.28
MPC		0.44
ClinPred		0.076	T
GERP RS		-12
Varity_R		0.15
gMVP		0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs200068830; hg19: chr16-30510662;