chr16-30481502-C-A

Variant names:

• chr16-30481502-C-A
• rs1064524
• NM_002209.3:c.640C>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_002209.3(ITGAL):​c.640C>A​(p.Arg214Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,760 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ITGAL NM_002209.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.80
• 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]

ENSG00000261346 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP7: Synonymous conserved (PhyloP=-3.8 with no splicing effect.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGAL	NM_002209.3	MANE Select	c.640C>A	p.Arg214Arg	synonymous	Exon 7 of 31	NP_002200.2
	ITGAL	NM_001114380.2		c.391C>A	p.Arg131Arg	synonymous	Exon 5 of 29	NP_001107852.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGAL	ENST00000356798.11	TSL:1 MANE Select	c.640C>A	p.Arg214Arg	synonymous	Exon 7 of 31	ENSP00000349252.5
	ITGAL	ENST00000358164.9	TSL:1	c.391C>A	p.Arg131Arg	synonymous	Exon 5 of 29	ENSP00000350886.5
	ITGAL	ENST00000562857.5	TSL:5	n.*20C>A		non_coding_transcript_exon	Exon 6 of 7	ENSP00000454342.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460760 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726708

African (AFR) AF: 0.00 AC: 0 AN: 33464

American (AMR) AF: 0.00 AC: 0 AN: 44666

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86146

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111138

Other (OTH) AF: 0.00 AC: 0 AN: 60346

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	0.12
DANN	Benign	0.53
PhyloP100		-3.8

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;