16-31363214-C-G

Variant names:

• chr16-31363214-C-G
• rs2230429
• NM_000887.5:c.1550C>G

Variant summary

Our verdict is Benign. The variant received -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 (★★).

• 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
• Publications: 43 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000887.5. 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
	ITGAX	NM_000887.5	MANE Select	c.1550C>G	p.Pro517Arg	missense	Exon 14 of 30	NP_000878.2
	ITGAX	NM_001286375.2		c.1550C>G	p.Pro517Arg	missense	Exon 14 of 31	NP_001273304.1	H3BN02

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGAX	ENST00000268296.9	TSL:1 MANE Select	c.1550C>G	p.Pro517Arg	missense	Exon 14 of 30	ENSP00000268296.5	P20702
	ITGAX	ENST00000562522.2	TSL:1	c.1550C>G	p.Pro517Arg	missense	Exon 14 of 31	ENSP00000454623.1	H3BN02
	ITGAX	ENST00000958326.1		c.1505C>G	p.Pro502Arg	missense	Exon 14 of 30	ENSP00000628385.1

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

GnomAD2 exomes AF: 0.341 AC: 85350 AN: 250316 AF XY: 0.336

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 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

African (AFR) AF: 0.134 AC: 4489 AN: 33414

American (AMR) AF: 0.336 AC: 14969 AN: 44550

Ashkenazi Jewish (ASJ) AF: 0.489 AC: 12734 AN: 26016

East Asian (EAS) AF: 0.767 AC: 30452 AN: 39688

South Asian (SAS) AF: 0.163 AC: 14032 AN: 86214

European-Finnish (FIN) AF: 0.324 AC: 17278 AN: 53392

Middle Eastern (MID) AF: 0.461 AC: 2656 AN: 5756

European-Non Finnish (NFE) AF: 0.348 AC: 386586 AN: 1111544

Other (OTH) AF: 0.354 AC: 21385 AN: 60342

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

African (AFR) AF: 0.143 AC: 5896 AN: 41356

American (AMR) AF: 0.309 AC: 4703 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.495 AC: 1714 AN: 3466

East Asian (EAS) AF: 0.703 AC: 3606 AN: 5132

South Asian (SAS) AF: 0.156 AC: 749 AN: 4816

European-Finnish (FIN) AF: 0.322 AC: 3402 AN: 10558

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.347 AC: 23532 AN: 67884

Other (OTH) AF: 0.353 AC: 742 AN: 2104

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

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
MetaRNN	Benign	0.000042	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		1.7
PrimateAI	Benign	0.48	T
PROVEAN	Pathogenic	-8.1	D
REVEL	Benign	0.14
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.33	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
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2230429; hg19: chr16-31374535; COSMIC: COSV51641424; COSMIC: COSV51641424;