rs235328

Variant names:

• chr21-44894042-G-C
• rs235328
• NM_000211.5:c.1084-498C>G

Variant summary

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

The NM_000211.5(ITGB2):​c.1084-498C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 250,374 control chromosomes in the GnomAD database, including 8,216 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 0.26 (5278 hom., cov: 32)
  • Exomes 𝑓: 0.23 (2938 hom.)
• Consequence: ITGB2 NM_000211.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.07

Genes affected

ITGB2 (HGNC:6155): (integrin subunit beta 2) This gene encodes an integrin beta chain, which combines with multiple different alpha chains to form different integrin heterodimers. Integrins are integral cell-surface proteins that participate in cell adhesion as well as cell-surface mediated signalling. The encoded protein plays an important role in immune response and defects in this gene cause leukocyte adhesion deficiency. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGB2	NM_000211.5	c.1084-498C>G		intron_variant	Intron 9 of 15	ENST00000652462.1	NP_000202.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGB2	ENST00000652462.1	c.1084-498C>G		intron_variant	Intron 9 of 15		NM_000211.5	ENSP00000498780.1

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39487 AN: 151742 Hom.: 5272 Cov.: 32

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.260

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.321

Gnomad MID AF: 0.178

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.237

GnomAD4 exome AF: 0.232 AC: 22840 AN: 98514 Hom.: 2938 Cov.: 0 AF XY: 0.229 AC XY: 12042 AN XY: 52692

Gnomad4 AFR exome AF: 0.315

Gnomad4 AMR exome AF: 0.185

Gnomad4 ASJ exome AF: 0.208

Gnomad4 EAS exome AF: 0.250

Gnomad4 SAS exome AF: 0.212

Gnomad4 FIN exome AF: 0.308

Gnomad4 NFE exome AF: 0.230

Gnomad4 OTH exome AF: 0.242

GnomAD4 genome AF: 0.260 AC: 39522 AN: 151860 Hom.: 5278 Cov.: 32 AF XY: 0.260 AC XY: 19328 AN XY: 74202

Gnomad4 AFR AF: 0.313

Gnomad4 AMR AF: 0.184

Gnomad4 ASJ AF: 0.220

Gnomad4 EAS AF: 0.260

Gnomad4 SAS AF: 0.236

Gnomad4 FIN AF: 0.321

Gnomad4 NFE AF: 0.243

Gnomad4 OTH AF: 0.239

Alfa AF: 0.254 Hom.: 593

Bravo AF: 0.255

Asia WGS AF: 0.272 AC: 948 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	6.8
DANN	Benign	0.66

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: rs235328; hg19: chr21-46313957;