NM_000887.5:c.247+129T>C

Variant names:

• chr16-31356857-T-C
• rs7190997
• NM_000887.5:c.247+129T>C

Variant summary

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

The NM_000887.5(ITGAX):​c.247+129T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 818,280 control chromosomes in the GnomAD database, including 117,865 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 0.52 (20921 hom., cov: 30)
  • Exomes 𝑓: 0.53 (96944 hom.)
• Consequence: ITGAX NM_000887.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.565
• Publications: 31 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 (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.685 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGAX	NM_000887.5	MANE Select	c.247+129T>C		intron	N/A	NP_000878.2
	ITGAX	NM_001286375.2		c.247+129T>C		intron	N/A	NP_001273304.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGAX	ENST00000268296.9	TSL:1 MANE Select	c.247+129T>C		intron	N/A	ENSP00000268296.5
	ITGAX	ENST00000562522.2	TSL:1	c.247+129T>C		intron	N/A	ENSP00000454623.1
	ITGAX	ENST00000567409.1	TSL:1	n.314+129T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.521 AC: 79038 AN: 151696 Hom.: 20908 Cov.: 30

Gnomad AFR AF: 0.495

Gnomad AMI AF: 0.539

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.722

Gnomad EAS AF: 0.703

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.476

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.529

Gnomad OTH AF: 0.588

GnomAD4 exome AF: 0.531 AC: 353750 AN: 666466 Hom.: 96944 Cov.: 9 AF XY: 0.528 AC XY: 182199 AN XY: 344808

African (AFR) AF: 0.496 AC: 8228 AN: 16598

American (AMR) AF: 0.486 AC: 10755 AN: 22144

Ashkenazi Jewish (ASJ) AF: 0.714 AC: 11448 AN: 16036

East Asian (EAS) AF: 0.770 AC: 24874 AN: 32310

South Asian (SAS) AF: 0.440 AC: 24314 AN: 55230

European-Finnish (FIN) AF: 0.473 AC: 16151 AN: 34148

Middle Eastern (MID) AF: 0.734 AC: 1834 AN: 2498

European-Non Finnish (NFE) AF: 0.523 AC: 237661 AN: 454178

Other (OTH) AF: 0.555 AC: 18485 AN: 33324

GnomAD4 genome AF: 0.521 AC: 79093 AN: 151814 Hom.: 20921 Cov.: 30 AF XY: 0.519 AC XY: 38493 AN XY: 74188

African (AFR) AF: 0.495 AC: 20503 AN: 41394

American (AMR) AF: 0.494 AC: 7542 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.722 AC: 2504 AN: 3470

East Asian (EAS) AF: 0.704 AC: 3604 AN: 5118

South Asian (SAS) AF: 0.429 AC: 2060 AN: 4806

European-Finnish (FIN) AF: 0.476 AC: 5017 AN: 10546

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.529 AC: 35916 AN: 67892

Other (OTH) AF: 0.588 AC: 1242 AN: 2112

Alfa AF: 0.541 Hom.: 28661

Bravo AF: 0.527

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.0
DANN	Benign	0.38
PhyloP100		0.56
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: rs7190997; hg19: chr16-31368178;