chr21-44913887-T-G

Position:

• chr21-44913887-T-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
ITGB2	NM_000211.5	c.-3-3102A>C		intron_variant		ENST00000652462.1	NP_000202.3
ITGB2	NM_001127491.3	c.-3-3102A>C		intron_variant			NP_001120963.2
ITGB2	NM_001303238.2	c.-253-3102A>C		intron_variant			NP_001290167.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGB2	ENST00000652462.1	c.-3-3102A>C		intron_variant			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

Gnomad4 AFR AF: 0.680

Gnomad4 AMR AF: 0.869

Gnomad4 ASJ AF: 0.855

Gnomad4 EAS AF: 0.723

Gnomad4 SAS AF: 0.907

Gnomad4 FIN AF: 0.804

Gnomad4 NFE AF: 0.838

Gnomad4 OTH AF: 0.811

Alfa AF: 0.831 Hom.: 20754

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3788150; hg19: chr21-46333802;