16-31382223-C-T

Variant names:

• chr16-31382223-C-T
• rs9929832
• NM_000887.5:c.*316C>T

Variant summary

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

The NM_000887.5(ITGAX):​c.*316C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.519 in 1,213,278 control chromosomes in the GnomAD database, including 173,668 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 0.58 (26169 hom., cov: 27)
  • Exomes 𝑓: 0.51 (147499 hom.)
• Consequence: ITGAX NM_000887.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.43
• Publications: 7 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.761 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGAX	NM_000887.5	c.*316C>T		3_prime_UTR_variant	Exon 30 of 30	ENST00000268296.9	NP_000878.2
ITGAX	XM_024450263.2	c.*316C>T		3_prime_UTR_variant	Exon 23 of 23		XP_024306031.1
ITGAX	NM_001286375.2	c.3482-245C>T		intron_variant	Intron 30 of 30		NP_001273304.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGAX	ENST00000268296.9	c.*316C>T		3_prime_UTR_variant	Exon 30 of 30	1	NM_000887.5	ENSP00000268296.5
ITGAX	ENST00000562522.2	c.3482-245C>T		intron_variant	Intron 30 of 30	1		ENSP00000454623.1
ITGAX	ENST00000571644.1	n.3673C>T		non_coding_transcript_exon_variant	Exon 22 of 22	2

Frequencies

GnomAD3 genomes AF: 0.578 AC: 85377 AN: 147668 Hom.: 26133 Cov.: 27

Gnomad AFR AF: 0.768

Gnomad AMI AF: 0.622

Gnomad AMR AF: 0.481

Gnomad ASJ AF: 0.438

Gnomad EAS AF: 0.762

Gnomad SAS AF: 0.544

Gnomad FIN AF: 0.479

Gnomad MID AF: 0.406

Gnomad NFE AF: 0.498

Gnomad OTH AF: 0.524

GnomAD4 exome AF: 0.511 AC: 544308 AN: 1065568 Hom.: 147499 Cov.: 16 AF XY: 0.510 AC XY: 262891 AN XY: 515532

African (AFR) AF: 0.769 AC: 16810 AN: 21862

American (AMR) AF: 0.446 AC: 5785 AN: 12980

Ashkenazi Jewish (ASJ) AF: 0.404 AC: 5979 AN: 14796

East Asian (EAS) AF: 0.792 AC: 16400 AN: 20720

South Asian (SAS) AF: 0.536 AC: 26548 AN: 49546

European-Finnish (FIN) AF: 0.428 AC: 8356 AN: 19524

Middle Eastern (MID) AF: 0.390 AC: 1126 AN: 2886

European-Non Finnish (NFE) AF: 0.501 AC: 441164 AN: 880518

Other (OTH) AF: 0.518 AC: 22140 AN: 42736

GnomAD4 genome AF: 0.578 AC: 85441 AN: 147710 Hom.: 26169 Cov.: 27 AF XY: 0.574 AC XY: 41098 AN XY: 71606

African (AFR) AF: 0.768 AC: 30752 AN: 40032

American (AMR) AF: 0.481 AC: 7049 AN: 14644

Ashkenazi Jewish (ASJ) AF: 0.438 AC: 1517 AN: 3462

East Asian (EAS) AF: 0.763 AC: 3768 AN: 4938

South Asian (SAS) AF: 0.544 AC: 2580 AN: 4744

European-Finnish (FIN) AF: 0.479 AC: 4403 AN: 9198

Middle Eastern (MID) AF: 0.388 AC: 111 AN: 286

European-Non Finnish (NFE) AF: 0.498 AC: 33610 AN: 67438

Other (OTH) AF: 0.527 AC: 1086 AN: 2060

Alfa AF: 0.506 Hom.: 22762

Asia WGS AF: 0.630 AC: 2155 AN: 3422

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.17
DANN	Benign	0.49
PhyloP100		-3.4
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: rs9929832; hg19: chr16-31393544;