rs1041457

Positions:

• chr21-44901903-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000211.5(ITGB2):​c.500-170T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 710,714 control chromosomes in the GnomAD database, including 43,650 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.37 (11001 hom., cov: 34)
  • Exomes 𝑓: 0.33 (32649 hom.)
• Consequence: ITGB2 NM_000211.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.03

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BP6: Variant 21-44901903-A-G is Benign according to our data. Variant chr21-44901903-A-G is described in ClinVar as [Benign]. Clinvar id is 1276148.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.424 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGB2	NM_000211.5	c.500-170T>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.500-170T>C		intron_variant			NM_000211.5	ENSP00000498780.1

Frequencies

GnomAD3 genomes AF: 0.374 AC: 56887 AN: 151938 Hom.: 10991 Cov.: 34

Gnomad AFR AF: 0.429

Gnomad AMI AF: 0.520

Gnomad AMR AF: 0.397

Gnomad ASJ AF: 0.435

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.361

Gnomad OTH AF: 0.362

GnomAD4 exome AF: 0.332 AC: 185369 AN: 558658 Hom.: 32649 AF XY: 0.329 AC XY: 94834 AN XY: 288070

Gnomad4 AFR exome AF: 0.432

Gnomad4 AMR exome AF: 0.375

Gnomad4 ASJ exome AF: 0.433

Gnomad4 EAS exome AF: 0.155

Gnomad4 SAS exome AF: 0.259

Gnomad4 FIN exome AF: 0.341

Gnomad4 NFE exome AF: 0.343

Gnomad4 OTH exome AF: 0.354

GnomAD4 genome AF: 0.374 AC: 56933 AN: 152056 Hom.: 11001 Cov.: 34 AF XY: 0.370 AC XY: 27522 AN XY: 74318

Gnomad4 AFR AF: 0.429

Gnomad4 AMR AF: 0.397

Gnomad4 ASJ AF: 0.435

Gnomad4 EAS AF: 0.184

Gnomad4 SAS AF: 0.241

Gnomad4 FIN AF: 0.337

Gnomad4 NFE AF: 0.361

Gnomad4 OTH AF: 0.358

Alfa AF: 0.369 Hom.: 9249

Bravo AF: 0.383

Asia WGS AF: 0.231 AC: 807 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 12, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.52
DANN	Benign	0.39

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: rs1041457; hg19: chr21-46321818; COSMIC: COSV56609896; COSMIC: COSV56609896;