chr21-44913887-T-G

Variant names:

• chr21-44913887-T-G
• rs3788150
• NM_000211.5:c.-3-3102A>C

Variant summary

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

The NM_000211.5(ITGB2):​c.-3-3102A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.793 in 152,198 control chromosomes in the GnomAD database, including 48,371 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 0.79 (48371 hom., cov: 34)
• Consequence: ITGB2 NM_000211.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.70
• Publications: 16 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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.884 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGB2	NM_000211.5	c.-3-3102A>C		intron_variant	Intron 1 of 15	ENST00000652462.1	NP_000202.3
ITGB2	NM_001127491.3	c.-3-3102A>C		intron_variant	Intron 1 of 15		NP_001120963.2
ITGB2	NM_001303238.2	c.-253-3102A>C		intron_variant	Intron 1 of 15		NP_001290167.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGB2	ENST00000652462.1	c.-3-3102A>C		intron_variant	Intron 1 of 15		NM_000211.5	ENSP00000498780.1

Frequencies

GnomAD3 genomes AF: 0.794 AC: 120685 AN: 152080 Hom.: 48341 Cov.: 34

Gnomad AFR AF: 0.680

Gnomad AMI AF: 0.795

Gnomad AMR AF: 0.869

Gnomad ASJ AF: 0.855

Gnomad EAS AF: 0.722

Gnomad SAS AF: 0.906

Gnomad FIN AF: 0.804

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.838

Gnomad OTH AF: 0.811

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

GnomAD4 genome AF: 0.793 AC: 120756 AN: 152198 Hom.: 48371 Cov.: 34 AF XY: 0.796 AC XY: 59195 AN XY: 74412

African (AFR) AF: 0.680 AC: 28206 AN: 41502

American (AMR) AF: 0.869 AC: 13296 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.855 AC: 2964 AN: 3468

East Asian (EAS) AF: 0.723 AC: 3734 AN: 5168

South Asian (SAS) AF: 0.907 AC: 4377 AN: 4828

European-Finnish (FIN) AF: 0.804 AC: 8535 AN: 10618

Middle Eastern (MID) AF: 0.796 AC: 234 AN: 294

European-Non Finnish (NFE) AF: 0.838 AC: 56972 AN: 68000

Other (OTH) AF: 0.811 AC: 1713 AN: 2112

Alfa AF: 0.831 Hom.: 29496

Bravo AF: 0.788

Asia WGS AF: 0.831 AC: 2890 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.7
DANN	Benign	0.45
PhyloP100		-1.7
PromoterAI		-0.0063	Neutral
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: rs3788150; hg19: chr21-46333802;