rs11702770

Variant names:

• chr21-44924915-A-G
• rs11702770
• ENST00000441379.5:n.278-1953A>G

Variant summary

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

The ENST00000441379.5(ITGB2-AS1):​n.278-1953A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 152,060 control chromosomes in the GnomAD database, including 5,595 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 0.27 (5595 hom., cov: 31)
• Consequence: ITGB2-AS1 ENST00000441379.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.276
• Publications: 0 publications found

Genes affected

ITGB2-AS1 (HGNC:44304): (ITGB2 antisense RNA 1)

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGB2	NM_001127491.3	c.-4+3739T>C		intron_variant	Intron 1 of 15		NP_001120963.2
ITGB2-AS1	NR_038311.1	n.388+1932A>G		intron_variant	Intron 2 of 4
ITGB2-AS1	NR_038312.1	n.388+1932A>G		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGB2-AS1	ENST00000441379.5	n.278-1953A>G		intron_variant	Intron 1 of 3	1
ITGB2	ENST00000355153.8	c.-4+3739T>C		intron_variant	Intron 1 of 15	2		ENSP00000347279.4
ITGB2	ENST00000397850.6	c.-234+3739T>C		intron_variant	Intron 1 of 16	5		ENSP00000380948.2

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40626 AN: 151942 Hom.: 5574 Cov.: 31

Gnomad AFR AF: 0.298

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.305

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.325

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.260

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.268 AC: 40700 AN: 152060 Hom.: 5595 Cov.: 31 AF XY: 0.265 AC XY: 19691 AN XY: 74316

African (AFR) AF: 0.298 AC: 12361 AN: 41422

American (AMR) AF: 0.321 AC: 4908 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.278 AC: 963 AN: 3470

East Asian (EAS) AF: 0.104 AC: 537 AN: 5178

South Asian (SAS) AF: 0.306 AC: 1475 AN: 4826

European-Finnish (FIN) AF: 0.196 AC: 2075 AN: 10582

Middle Eastern (MID) AF: 0.322 AC: 94 AN: 292

European-Non Finnish (NFE) AF: 0.256 AC: 17405 AN: 67986

Other (OTH) AF: 0.262 AC: 554 AN: 2112

Alfa AF: 0.263 Hom.: 2261

Bravo AF: 0.280

Asia WGS AF: 0.219 AC: 760 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.7
DANN	Benign	0.30
PhyloP100		-0.28
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11702770; hg19: chr21-46344830;