16-31363214-C-G

Position:

• chr16-31363214-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000887.5(ITGAX):​c.1550C>G​(p.Pro517Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 1,612,670 control chromosomes in the GnomAD database, including 101,517 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.30 (7728 hom., cov: 31)
  • Exomes 𝑓: 0.35 (93789 hom.)
• Consequence: ITGAX NM_000887.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.67

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=4.2136813E-5).
• BP6: Variant 16-31363214-C-G is Benign according to our data. Variant chr16-31363214-C-G is described in ClinVar as [Benign]. Clinvar id is 1290142.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.684 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGAX	NM_000887.5	c.1550C>G	p.Pro517Arg	missense_variant	14/30	ENST00000268296.9	NP_000878.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGAX	ENST00000268296.9	c.1550C>G	p.Pro517Arg	missense_variant	14/30	1	NM_000887.5	ENSP00000268296.5
ITGAX	ENST00000562522.2	c.1550C>G	p.Pro517Arg	missense_variant	14/31	1		ENSP00000454623.1
ITGAX	ENST00000571644.1	n.1571C>G		non_coding_transcript_exon_variant	7/22	2

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44794 AN: 151638 Hom.: 7727 Cov.: 31

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.342

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.495

Gnomad EAS AF: 0.702

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.322

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.354

GnomAD3 exomes AF: 0.341 AC: 85350 AN: 250316 Hom.: 16881 AF XY: 0.336 AC XY: 45459 AN XY: 135366

Gnomad AFR exome AF: 0.133

Gnomad AMR exome AF: 0.337

Gnomad ASJ exome AF: 0.489

Gnomad EAS exome AF: 0.693

Gnomad SAS exome AF: 0.162

Gnomad FIN exome AF: 0.327

Gnomad NFE exome AF: 0.352

Gnomad OTH exome AF: 0.354

GnomAD4 exome AF: 0.345 AC: 504581 AN: 1460916 Hom.: 93789 Cov.: 53 AF XY: 0.341 AC XY: 247758 AN XY: 726788

Gnomad4 AFR exome AF: 0.134

Gnomad4 AMR exome AF: 0.336

Gnomad4 ASJ exome AF: 0.489

Gnomad4 EAS exome AF: 0.767

Gnomad4 SAS exome AF: 0.163

Gnomad4 FIN exome AF: 0.324

Gnomad4 NFE exome AF: 0.348

Gnomad4 OTH exome AF: 0.354

GnomAD4 genome AF: 0.295 AC: 44793 AN: 151754 Hom.: 7728 Cov.: 31 AF XY: 0.294 AC XY: 21831 AN XY: 74174

Gnomad4 AFR AF: 0.143

Gnomad4 AMR AF: 0.309

Gnomad4 ASJ AF: 0.495

Gnomad4 EAS AF: 0.703

Gnomad4 SAS AF: 0.156

Gnomad4 FIN AF: 0.322

Gnomad4 NFE AF: 0.347

Gnomad4 OTH AF: 0.353

Alfa AF: 0.348 Hom.: 7295

Bravo AF: 0.298

TwinsUK AF: 0.345 AC: 1281

ALSPAC AF: 0.343 AC: 1323

ESP6500AA AF: 0.156 AC: 685

ESP6500EA AF: 0.365 AC: 3143

ExAC AF: 0.330 AC: 40097

Asia WGS AF: 0.374 AC: 1297 AN: 3478

EpiCase AF: 0.359

EpiControl AF: 0.372

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 18, 2020	This variant is associated with the following publications: (PMID: 25155097) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.60	D;.
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Benign	0.68	D
LIST_S2	Uncertain	0.94	D;D
MetaRNN	Benign	0.000042	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	3.0	M;.
PrimateAI	Benign	0.48	T
PROVEAN	Pathogenic	-8.1	D;D
REVEL	Benign	0.14
Sift	Uncertain	0.0030	D;D
Sift4G	Benign	0.33	T;T
Polyphen		1.0	D;.
Vest4		0.44
MPC		0.79
ClinPred		0.060	T
GERP RS		4.0
Varity_R		0.64
gMVP		0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs2230429; hg19: chr16-31374535; COSMIC: COSV51641424; COSMIC: COSV51641424;