rs5030670

Variant names:

• chr21-44900488-C-T
• rs5030670
• NM_000211.5:c.742-13G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000211.5(ITGB2):​c.742-13G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 1,613,112 control chromosomes in the GnomAD database, including 18,231 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1291 hom., cov: 33)
  • Exomes 𝑓: 0.15 (16940 hom.)
• Consequence: ITGB2 NM_000211.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7 O:1
• Conservation: PhyloP100: -1.84
• Publications: 8 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, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 21-44900488-C-T is Benign according to our data. Variant chr21-44900488-C-T is described in ClinVar as Benign. ClinVar VariationId is 100760.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000211.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB2	NM_000211.5	MANE Select	c.742-13G>A		intron	N/A	NP_000202.3	P05107
	ITGB2	NM_001127491.3		c.742-13G>A		intron	N/A	NP_001120963.2	P05107
	ITGB2	NM_001303238.2		c.535-13G>A		intron	N/A	NP_001290167.1	B4E0R1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB2	ENST00000652462.1	MANE Select	c.742-13G>A		intron	N/A	ENSP00000498780.1	A0A494C0X7
	ITGB2	ENST00000302347.10	TSL:1	c.742-13G>A		intron	N/A	ENSP00000303242.6	A0AAA9WZN5
	ITGB2	ENST00000397852.5	TSL:1	c.742-13G>A		intron	N/A	ENSP00000380950.1	P05107

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18424 AN: 152084 Hom.: 1291 Cov.: 33

Gnomad AFR AF: 0.0644

Gnomad AMI AF: 0.108

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.0288

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.142

GnomAD2 exomes AF: 0.124 AC: 31148 AN: 250310 AF XY: 0.128

Gnomad AFR exome AF: 0.0597

Gnomad AMR exome AF: 0.0692

Gnomad ASJ exome AF: 0.136

Gnomad EAS exome AF: 0.0302

Gnomad FIN exome AF: 0.177

Gnomad NFE exome AF: 0.162

Gnomad OTH exome AF: 0.133

GnomAD4 exome AF: 0.148 AC: 215805 AN: 1460910 Hom.: 16940 Cov.: 35 AF XY: 0.147 AC XY: 106668 AN XY: 726742

African (AFR) AF: 0.0589 AC: 1970 AN: 33468

American (AMR) AF: 0.0723 AC: 3234 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 3494 AN: 26126

East Asian (EAS) AF: 0.0228 AC: 905 AN: 39694

South Asian (SAS) AF: 0.0954 AC: 8224 AN: 86234

European-Finnish (FIN) AF: 0.173 AC: 9211 AN: 53250

Middle Eastern (MID) AF: 0.110 AC: 604 AN: 5476

European-Non Finnish (NFE) AF: 0.162 AC: 179987 AN: 1111612

Other (OTH) AF: 0.135 AC: 8176 AN: 60342

GnomAD4 genome AF: 0.121 AC: 18419 AN: 152202 Hom.: 1291 Cov.: 33 AF XY: 0.120 AC XY: 8914 AN XY: 74408

African (AFR) AF: 0.0643 AC: 2673 AN: 41556

American (AMR) AF: 0.101 AC: 1548 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 465 AN: 3468

East Asian (EAS) AF: 0.0289 AC: 149 AN: 5164

South Asian (SAS) AF: 0.0999 AC: 482 AN: 4824

European-Finnish (FIN) AF: 0.176 AC: 1866 AN: 10598

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.159 AC: 10806 AN: 67978

Other (OTH) AF: 0.140 AC: 296 AN: 2114

Alfa AF: 0.140 Hom.: 2622

Bravo AF: 0.113

Asia WGS AF: 0.0560 AC: 194 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Leukocyte adhesion deficiency 1 (4)
-	-	2	not provided (2)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.11
DANN	Benign	0.59
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs5030670; hg19: chr21-46320403; COSMIC: COSV56610895; COSMIC: COSV56610895;