NM_000211.5:c.148-1089A>G

Variant names:

• chr21-44908184-T-C
• rs760462
• NM_000211.5:c.148-1089A>G

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.148-1089A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.847 in 719,108 control chromosomes in the GnomAD database, including 259,384 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.87 (58166 hom., cov: 31)
  • Exomes 𝑓: 0.84 (201218 hom.)
• Consequence: ITGB2 NM_000211.5 intron
• Scores: Splicing: ADA: 0.00002529
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -3.48
• Publications: 42 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

LOC107987303 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_addAF=-0.906843).
• BP6: Variant 21-44908184-T-C is Benign according to our data. Variant chr21-44908184-T-C is described in ClinVar as Benign. ClinVar VariationId is 803634.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.959 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB2	NM_000211.5	MANE Select	c.148-1089A>G		intron	N/A	NP_000202.3
	ITGB2	NM_001127491.3		c.148-1089A>G		intron	N/A	NP_001120963.2
	ITGB2	NM_001303238.2		c.-60-1089A>G		intron	N/A	NP_001290167.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB2	ENST00000652462.1	MANE Select	c.148-1089A>G		intron	N/A	ENSP00000498780.1
	ITGB2	ENST00000302347.10	TSL:1	c.148-1089A>G		intron	N/A	ENSP00000303242.6
	ITGB2	ENST00000397852.5	TSL:1	c.148-1089A>G		intron	N/A	ENSP00000380950.1

Frequencies

GnomAD3 genomes AF: 0.872 AC: 132527 AN: 152022 Hom.: 58100 Cov.: 31

Gnomad AFR AF: 0.967

Gnomad AMI AF: 0.787

Gnomad AMR AF: 0.894

Gnomad ASJ AF: 0.863

Gnomad EAS AF: 0.773

Gnomad SAS AF: 0.921

Gnomad FIN AF: 0.798

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.826

Gnomad OTH AF: 0.863

GnomAD2 exomes AF: 0.851 AC: 157890 AN: 185526 AF XY: 0.850

Gnomad AFR exome AF: 0.970

Gnomad AMR exome AF: 0.928

Gnomad ASJ exome AF: 0.859

Gnomad EAS exome AF: 0.764

Gnomad FIN exome AF: 0.786

Gnomad NFE exome AF: 0.823

Gnomad OTH exome AF: 0.850

GnomAD4 exome AF: 0.841 AC: 476683 AN: 566968 Hom.: 201218 Cov.: 0 AF XY: 0.844 AC XY: 258338 AN XY: 306226

African (AFR) AF: 0.967 AC: 15627 AN: 16156

American (AMR) AF: 0.923 AC: 31946 AN: 34622

Ashkenazi Jewish (ASJ) AF: 0.863 AC: 16517 AN: 19142

East Asian (EAS) AF: 0.756 AC: 25861 AN: 34190

South Asian (SAS) AF: 0.910 AC: 57255 AN: 62894

European-Finnish (FIN) AF: 0.796 AC: 39107 AN: 49110

Middle Eastern (MID) AF: 0.860 AC: 3347 AN: 3892

European-Non Finnish (NFE) AF: 0.825 AC: 261387 AN: 316652

Other (OTH) AF: 0.846 AC: 25636 AN: 30310

GnomAD4 genome AF: 0.872 AC: 132651 AN: 152140 Hom.: 58166 Cov.: 31 AF XY: 0.872 AC XY: 64848 AN XY: 74360

African (AFR) AF: 0.967 AC: 40170 AN: 41538

American (AMR) AF: 0.895 AC: 13670 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.863 AC: 2995 AN: 3472

East Asian (EAS) AF: 0.773 AC: 3980 AN: 5146

South Asian (SAS) AF: 0.921 AC: 4435 AN: 4818

European-Finnish (FIN) AF: 0.798 AC: 8432 AN: 10568

Middle Eastern (MID) AF: 0.844 AC: 248 AN: 294

European-Non Finnish (NFE) AF: 0.826 AC: 56184 AN: 67998

Other (OTH) AF: 0.861 AC: 1821 AN: 2114

Alfa AF: 0.852 Hom.: 125195

Bravo AF: 0.879

TwinsUK AF: 0.819 AC: 3038

ALSPAC AF: 0.819 AC: 3156

ESP6500AA AF: 0.975 AC: 1666

ESP6500EA AF: 0.831 AC: 3260

ExAC AF: 0.831 AC: 91552

Asia WGS AF: 0.879 AC: 3058 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.91	T
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.54
DANN	Benign	0.31
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0012	N
PhyloP100		-3.5
GERP RS		-2.3
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000025
dbscSNV1_RF	Benign	0.0
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: rs760462; hg19: chr21-46328099;