rs235328

Variant names:

• chr21-44894042-G-C
• rs235328
• ENST00000498666.5:n.2155C>G

Variant summary

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

The ENST00000498666.5(ITGB2):​n.2155C>G 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 0.249 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 ENST00000498666.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.07
• Publications: 3 publications found

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]

ITGB2 Gene-Disease associations (from GenCC):

• leukocyte adhesion deficiency 1

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000498666.5. 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
	ITGB2	NM_000211.5	MANE Select	c.1084-498C>G		intron	N/A	NP_000202.3
	ITGB2	NM_001127491.3		c.1084-498C>G		intron	N/A	NP_001120963.2
	ITGB2	NM_001303238.2		c.877-498C>G		intron	N/A	NP_001290167.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB2	ENST00000498666.5	TSL:1	n.2155C>G		non_coding_transcript_exon	Exon 9 of 15
	ITGB2	ENST00000652462.1	MANE Select	c.1084-498C>G		intron	N/A	ENSP00000498780.1
	ITGB2	ENST00000302347.10	TSL:1	c.1156-498C>G		intron	N/A	ENSP00000303242.6

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

African (AFR) AF: 0.315 AC: 1166 AN: 3706

American (AMR) AF: 0.185 AC: 952 AN: 5150

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 468 AN: 2248

East Asian (EAS) AF: 0.250 AC: 1338 AN: 5350

South Asian (SAS) AF: 0.212 AC: 3561 AN: 16812

European-Finnish (FIN) AF: 0.308 AC: 1191 AN: 3872

Middle Eastern (MID) AF: 0.173 AC: 68 AN: 394

European-Non Finnish (NFE) AF: 0.230 AC: 12890 AN: 56004

Other (OTH) AF: 0.242 AC: 1206 AN: 4978

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

African (AFR) AF: 0.313 AC: 12946 AN: 41316

American (AMR) AF: 0.184 AC: 2803 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 763 AN: 3468

East Asian (EAS) AF: 0.260 AC: 1344 AN: 5170

South Asian (SAS) AF: 0.236 AC: 1134 AN: 4814

European-Finnish (FIN) AF: 0.321 AC: 3385 AN: 10558

Middle Eastern (MID) AF: 0.185 AC: 54 AN: 292

European-Non Finnish (NFE) AF: 0.243 AC: 16535 AN: 67966

Other (OTH) AF: 0.239 AC: 503 AN: 2106

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	6.8
DANN	Benign	0.66
PhyloP100		1.1
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: rs235328; hg19: chr21-46313957;