chr16-31357553-T-C

Variant names:

• chr16-31357553-T-C
• rs11574637
• ENST00000567409.1:n.837T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000567409.1(ITGAX):​n.837T>C variant causes a non coding transcript exon 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 ENST00000567409.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.849
• Publications: 63 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 -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000567409.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGAX	NM_000887.5	MANE Select	c.430+189T>C		intron	N/A	NP_000878.2
	ITGAX	NM_001286375.2		c.430+189T>C		intron	N/A	NP_001273304.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGAX	ENST00000567409.1	TSL:1	n.837T>C		non_coding_transcript_exon	Exon 4 of 4
	ITGAX	ENST00000268296.9	TSL:1 MANE Select	c.430+189T>C		intron	N/A	ENSP00000268296.5
	ITGAX	ENST00000562522.2	TSL:1	c.430+189T>C		intron	N/A	ENSP00000454623.1

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

African (AFR) AF: 0.293 AC: 3340 AN: 11416

American (AMR) AF: 0.147 AC: 2375 AN: 16162

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 2905 AN: 13284

East Asian (EAS) AF: 0.00168 AC: 49 AN: 29122

South Asian (SAS) AF: 0.268 AC: 10600 AN: 39602

European-Finnish (FIN) AF: 0.147 AC: 4334 AN: 29514

Middle Eastern (MID) AF: 0.291 AC: 559 AN: 1922

European-Non Finnish (NFE) AF: 0.177 AC: 45316 AN: 256426

Other (OTH) AF: 0.188 AC: 4687 AN: 24922

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

African (AFR) AF: 0.293 AC: 12172 AN: 41490

American (AMR) AF: 0.177 AC: 2703 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.225 AC: 781 AN: 3470

East Asian (EAS) AF: 0.00985 AC: 51 AN: 5176

South Asian (SAS) AF: 0.270 AC: 1304 AN: 4824

European-Finnish (FIN) AF: 0.150 AC: 1592 AN: 10600

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.176 AC: 11972 AN: 67952

Other (OTH) AF: 0.220 AC: 465 AN: 2112

Alfa AF: 0.185 Hom.: 12125

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.64
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
PhyloP100		-0.85
Sift4G	Pathogenic	0.0	D
Vest4		0.039
MVP		0.40
GERP RS		-2.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11574637; hg19: chr16-31368874;