rs1447960807

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr16-30499154-A-G
• chr16-30499154-A-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>G​(p.Tyr638Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,778 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ITGAL NM_002209.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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=0.24214065).

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>G	p.Tyr638Cys	missense	Exon 16 of 31	NP_002200.2	P20701-1
	ITGAL	NM_001114380.2		c.1664A>G	p.Tyr555Cys	missense	Exon 14 of 29	NP_001107852.1	P20701-3
	ITGAL-AS1	NR_186415.1		n.192-3T>C		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>G	p.Tyr638Cys	missense	Exon 16 of 31	ENSP00000349252.5	P20701-1
	ITGAL	ENST00000358164.9	TSL:1	c.1664A>G	p.Tyr555Cys	missense	Exon 14 of 29	ENSP00000350886.5	P20701-3
	ITGAL	ENST00000955586.1		c.1919A>G	p.Tyr640Cys	missense	Exon 16 of 31	ENSP00000625645.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152002 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251462 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461776 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727192

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

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

American (AMR) AF: 0.0000224 AC: 1 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

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000203476), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152002 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74268

African (AFR) AF: 0.0000242 AC: 1 AN: 41378

American (AMR) AF: 0.00 AC: 0 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67974

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000658 Hom.: 0

Bravo AF: 0.0000151

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T
Eigen	Benign	-0.063
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.024	N
LIST_S2	Uncertain	0.87	D
M_CAP	Uncertain	0.092	D
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		0.36
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.11
Sift	Benign	0.083	T
Sift4G	Benign	0.12	T
Polyphen		0.96	D
Vest4		0.23
MutPred		0.48		Gain of catalytic residue at T640 (P = 0.0784)
MVP		0.76
MPC		0.80
ClinPred		0.62	D
GERP RS		2.6
Varity_R		0.38
gMVP		0.70

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: rs1447960807; hg19: chr16-30510475;