rs2929

Positions:

• chr16-31381987-G-A

Variant summary

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

The NM_000887.5(ITGAX):​c.*80G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 1,474,592 control chromosomes in the GnomAD database, including 39,157 homozygotes. 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: 𝑓 0.27 (5703 hom., cov: 26)
  • Exomes 𝑓: 0.22 (33454 hom.)
• Consequence: ITGAX NM_000887.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.141

Genes affected

ITGAX (HGNC:6152): (integrin subunit alpha X) This gene encodes the integrin alpha X chain protein. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain. This protein combines with the beta 2 chain (ITGB2) to form a leukocyte-specific integrin referred to as inactivated-C3b (iC3b) receptor 4 (CR4). The alpha X beta 2 complex seems to overlap the properties of the alpha M beta 2 integrin in the adherence of neutrophils and monocytes to stimulated endothelium cells, and in the phagocytosis of complement coated particles. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2013]

ITGAX (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.424 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGAX	NM_000887.5	c.*80G>A		3_prime_UTR_variant	30/30	ENST00000268296.9	NP_000878.2
ITGAX	XM_024450263.2	c.*80G>A		3_prime_UTR_variant	23/23		XP_024306031.1
ITGAX	NM_001286375.2	c.3481+91G>A		intron_variant			NP_001273304.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGAX	ENST00000268296.9	c.*80G>A		3_prime_UTR_variant	30/30	1	NM_000887.5	ENSP00000268296.5
ITGAX	ENST00000562522.2	c.3481+91G>A		intron_variant		1		ENSP00000454623.1
ITGAX	ENST00000571644.1	n.3437G>A		non_coding_transcript_exon_variant	22/22	2

Frequencies

GnomAD3 genomes AF: 0.275 AC: 38891 AN: 141454 Hom.: 5699 Cov.: 26

Gnomad AFR AF: 0.430

Gnomad AMI AF: 0.369

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.179

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.217

Gnomad NFE AF: 0.224

Gnomad OTH AF: 0.238

GnomAD4 exome AF: 0.221 AC: 294736 AN: 1333020 Hom.: 33454 Cov.: 21 AF XY: 0.220 AC XY: 144527 AN XY: 658026

Gnomad4 AFR exome AF: 0.425

Gnomad4 AMR exome AF: 0.139

Gnomad4 ASJ exome AF: 0.174

Gnomad4 EAS exome AF: 0.265

Gnomad4 SAS exome AF: 0.164

Gnomad4 FIN exome AF: 0.237

Gnomad4 NFE exome AF: 0.221

Gnomad4 OTH exome AF: 0.221

GnomAD4 genome AF: 0.275 AC: 38919 AN: 141572 Hom.: 5703 Cov.: 26 AF XY: 0.270 AC XY: 18584 AN XY: 68886

Gnomad4 AFR AF: 0.429

Gnomad4 AMR AF: 0.173

Gnomad4 ASJ AF: 0.179

Gnomad4 EAS AF: 0.204

Gnomad4 SAS AF: 0.172

Gnomad4 FIN AF: 0.255

Gnomad4 NFE AF: 0.224

Gnomad4 OTH AF: 0.238

Alfa AF: 0.215 Hom.: 7772

Bravo AF: 0.262

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.5
DANN	Benign	0.60

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: rs2929; hg19: chr16-31393308;