rs235325

Positions:

• chr21-44891349-A-G
• chr21-44891349-A-C

Variant summary

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

The NM_000211.5(ITGB2):​c.1412+460T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.637 in 152,040 control chromosomes in the GnomAD database, including 32,304 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 (32304 hom., cov: 34)
• Consequence: ITGB2 NM_000211.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.836 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGB2	NM_000211.5	c.1412+460T>C		intron_variant		ENST00000652462.1	NP_000202.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGB2	ENST00000652462.1	c.1412+460T>C		intron_variant			NM_000211.5	ENSP00000498780	P1

Frequencies

GnomAD3 genomes AF: 0.637 AC: 96758 AN: 151922 Hom.: 32268 Cov.: 34

Gnomad AFR AF: 0.843

Gnomad AMI AF: 0.507

Gnomad AMR AF: 0.481

Gnomad ASJ AF: 0.576

Gnomad EAS AF: 0.437

Gnomad SAS AF: 0.585

Gnomad FIN AF: 0.545

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.584

Gnomad OTH AF: 0.641

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

GnomAD4 genome AF: 0.637 AC: 96852 AN: 152040 Hom.: 32304 Cov.: 34 AF XY: 0.631 AC XY: 46850 AN XY: 74306

Gnomad4 AFR AF: 0.843

Gnomad4 AMR AF: 0.480

Gnomad4 ASJ AF: 0.576

Gnomad4 EAS AF: 0.437

Gnomad4 SAS AF: 0.586

Gnomad4 FIN AF: 0.545

Gnomad4 NFE AF: 0.584

Gnomad4 OTH AF: 0.641

Alfa AF: 0.594 Hom.: 30294

Bravo AF: 0.637

Asia WGS AF: 0.555 AC: 1933 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.68
DANN	Benign	0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs235325; hg19: chr21-46311264; COSMIC: COSV56608830; COSMIC: COSV56608830;