rs11574637

Variant names:

• chr16-31357553-T-C
• rs11574637
• NM_000887.5:c.430+189T>C

Variant summary

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

The NM_000887.5(ITGAX):​c.430+189T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 574,488 control chromosomes in the GnomAD database, including 11,148 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 0.21 (3573 hom., cov: 32)
  • Exomes 𝑓: 0.18 (7575 hom.)
• Consequence: ITGAX NM_000887.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.849

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 (MetaRNN=0.0015811622).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGAX	NM_000887.5	c.430+189T>C		intron_variant	Intron 5 of 29	ENST00000268296.9	NP_000878.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGAX	ENST00000268296.9	c.430+189T>C		intron_variant	Intron 5 of 29	1	NM_000887.5	ENSP00000268296.5
ITGAX	ENST00000562522.2	c.430+189T>C		intron_variant	Intron 5 of 30	1		ENSP00000454623.1
ITGAX	ENST00000567409.1	n.837T>C		non_coding_transcript_exon_variant	Exon 4 of 4	1
ITGAX	ENST00000562918.5	c.538T>C	p.Phe180Leu	missense_variant	Exon 5 of 5	2		ENSP00000483860.1

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31266 AN: 152000 Hom.: 3572 Cov.: 32

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.195

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.0100

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.218

GnomAD4 exome AF: 0.176 AC: 74165 AN: 422370 Hom.: 7575 Cov.: 3 AF XY: 0.180 AC XY: 39658 AN XY: 220568

Gnomad4 AFR exome AF: 0.293

Gnomad4 AMR exome AF: 0.147

Gnomad4 ASJ exome AF: 0.219

Gnomad4 EAS exome AF: 0.00168

Gnomad4 SAS exome AF: 0.268

Gnomad4 FIN exome AF: 0.147

Gnomad4 NFE exome AF: 0.177

Gnomad4 OTH exome AF: 0.188

GnomAD4 genome AF: 0.206 AC: 31301 AN: 152118 Hom.: 3573 Cov.: 32 AF XY: 0.205 AC XY: 15263 AN XY: 74394

Gnomad4 AFR AF: 0.293

Gnomad4 AMR AF: 0.177

Gnomad4 ASJ AF: 0.225

Gnomad4 EAS AF: 0.00985

Gnomad4 SAS AF: 0.270

Gnomad4 FIN AF: 0.150

Gnomad4 NFE AF: 0.176

Gnomad4 OTH AF: 0.220

Alfa AF: 0.183 Hom.: 5938

Bravo AF: 0.208

TwinsUK AF: 0.164 AC: 608

ALSPAC AF: 0.155 AC: 599

Asia WGS AF: 0.141 AC: 491 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.87	T
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.5
DANN	Benign	0.63
DEOGEN2	Benign	0.0069	T
FATHMM_MKL	Benign	0.0087	N
LIST_S2	Benign	0.22	T
MetaRNN	Benign	0.0016	T
Sift4G	Pathogenic	0.0	D
Vest4		0.039
MVP		0.40
GERP RS		-2.2

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: rs11574637; hg19: chr16-31368874;