chr16-30499154-A-C

Variant names:

• chr16-30499154-A-C
• rs1447960807
• NM_002209.3:c.1913A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002209.3(ITGAL):​c.1913A>C​(p.Tyr638Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,776 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. Y638C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ITGAL NM_002209.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.364
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20287144).

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.1913A>C	p.Tyr638Ser	missense	Exon 16 of 31	NP_002200.2	P20701-1
	ITGAL	NM_001114380.2		c.1664A>C	p.Tyr555Ser	missense	Exon 14 of 29	NP_001107852.1	P20701-3
	ITGAL-AS1	NR_186415.1		n.192-3T>G		splice_region intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGAL	ENST00000356798.11	TSL:1 MANE Select	c.1913A>C	p.Tyr638Ser	missense	Exon 16 of 31	ENSP00000349252.5	P20701-1
	ITGAL	ENST00000358164.9	TSL:1	c.1664A>C	p.Tyr555Ser	missense	Exon 14 of 29	ENSP00000350886.5	P20701-3
	ITGAL	ENST00000955586.1		c.1919A>C	p.Tyr640Ser	missense	Exon 16 of 31	ENSP00000625645.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461776 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727192

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111934

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.072	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	13
DANN	Benign	0.87
DEOGEN2	Benign	0.034	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.065	N
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.068	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		0.36
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.096
Sift	Benign	0.31	T
Sift4G	Benign	0.27	T
Polyphen		0.25	B
Vest4		0.45
MutPred		0.59		Gain of disorder (P = 0.005)
MVP		0.65
MPC		0.44
ClinPred		0.094	T
GERP RS		2.6
Varity_R		0.18
gMVP		0.69
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1447960807; hg19: chr16-30510475;