16-31382223-C-T

Position:

• chr16-31382223-C-T

Variant summary

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

The ENST00000268296.9(ITGAX):​c.*316C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.519 in 1,213,278 control chromosomes in the GnomAD database, including 173,668 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 0.58 (26169 hom., cov: 27)
  • Exomes 𝑓: 0.51 (147499 hom.)
• Consequence: ITGAX ENST00000268296.9 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.43

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.761 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGAX	NM_000887.5	c.*316C>T		3_prime_UTR_variant	30/30	ENST00000268296.9	NP_000878.2
ITGAX	XM_024450263.2	c.*316C>T		3_prime_UTR_variant	23/23		XP_024306031.1
ITGAX	NM_001286375.2	c.3482-245C>T		intron_variant			NP_001273304.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGAX	ENST00000268296.9	c.*316C>T		3_prime_UTR_variant	30/30	1	NM_000887.5	ENSP00000268296	P4
ITGAX	ENST00000562522.2	c.3482-245C>T		intron_variant		1		ENSP00000454623	A2
ITGAX	ENST00000571644.1	n.3673C>T		non_coding_transcript_exon_variant	22/22	2

Frequencies

GnomAD3 genomes AF: 0.578 AC: 85377 AN: 147668 Hom.: 26133 Cov.: 27

Gnomad AFR AF: 0.768

Gnomad AMI AF: 0.622

Gnomad AMR AF: 0.481

Gnomad ASJ AF: 0.438

Gnomad EAS AF: 0.762

Gnomad SAS AF: 0.544

Gnomad FIN AF: 0.479

Gnomad MID AF: 0.406

Gnomad NFE AF: 0.498

Gnomad OTH AF: 0.524

GnomAD4 exome AF: 0.511 AC: 544308 AN: 1065568 Hom.: 147499 Cov.: 16 AF XY: 0.510 AC XY: 262891 AN XY: 515532

Gnomad4 AFR exome AF: 0.769

Gnomad4 AMR exome AF: 0.446

Gnomad4 ASJ exome AF: 0.404

Gnomad4 EAS exome AF: 0.792

Gnomad4 SAS exome AF: 0.536

Gnomad4 FIN exome AF: 0.428

Gnomad4 NFE exome AF: 0.501

Gnomad4 OTH exome AF: 0.518

GnomAD4 genome AF: 0.578 AC: 85441 AN: 147710 Hom.: 26169 Cov.: 27 AF XY: 0.574 AC XY: 41098 AN XY: 71606

Gnomad4 AFR AF: 0.768

Gnomad4 AMR AF: 0.481

Gnomad4 ASJ AF: 0.438

Gnomad4 EAS AF: 0.763

Gnomad4 SAS AF: 0.544

Gnomad4 FIN AF: 0.479

Gnomad4 NFE AF: 0.498

Gnomad4 OTH AF: 0.527

Alfa AF: 0.502 Hom.: 18608

Asia WGS AF: 0.630 AC: 2155 AN: 3422

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.17
DANN	Benign	0.49

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: rs9929832; hg19: chr16-31393544;