rs760456

chr21-44909500-G-Cchr21-44909500-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000211.5(ITGB2):c.147+784C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.642 in 152,150 control chromosomes in the GnomAD database, including 31,656 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 0.64 (31623 hom., cov: 32)
  • Exomes 𝑓: 0.60 (33 hom.)
• Consequence: ITGB2 NM_000211.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0770

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]

LOC107987303 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGB2	NM_000211.5	c.147+784C>G		intron_variant		ENST00000652462.1
LOC107987303	XR_001755083.2	n.775C>G		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGB2	ENST00000652462.1	c.147+784C>G		intron_variant			NM_000211.5	P1

Frequencies

GnomAD3 genomes AF: 0.642 AC: 97567 AN: 151878 Hom.: 31598 Cov.: 32

Gnomad AFR AF: 0.599

Gnomad AMI AF: 0.768

Gnomad AMR AF: 0.702

Gnomad ASJ AF: 0.757

Gnomad EAS AF: 0.570

Gnomad SAS AF: 0.720

Gnomad FIN AF: 0.508

Gnomad MID AF: 0.739

Gnomad NFE AF: 0.667

Gnomad OTH AF: 0.684

GnomAD4 exome AF: 0.604 AC: 93 AN: 154 Hom.: 33 Cov.: 0 AF XY: 0.625 AC XY: 55 AN XY: 88

Gnomad4 AFR exome AF: 0.250

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.786

Gnomad4 FIN exome AF: 0.484

Gnomad4 NFE exome AF: 0.694

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.642 AC: 97638 AN: 151996 Hom.: 31623 Cov.: 32 AF XY: 0.639 AC XY: 47480 AN XY: 74296

Gnomad4 AFR AF: 0.599

Gnomad4 AMR AF: 0.703

Gnomad4 ASJ AF: 0.757

Gnomad4 EAS AF: 0.570

Gnomad4 SAS AF: 0.718

Gnomad4 FIN AF: 0.508

Gnomad4 NFE AF: 0.667

Gnomad4 OTH AF: 0.682

Alfa AF: 0.550 Hom.: 1668

Bravo AF: 0.650

Asia WGS AF: 0.652 AC: 2268 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	2.8
Dann	Benign	0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs760456; hg19: chr21-46329415;