21-44924511-A-G

Position:

• chr21-44924511-A-G

Variant summary

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

The NM_001127491.3(ITGB2):​c.-4+4143T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.55 in 152,050 control chromosomes in the GnomAD database, including 24,645 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 0.55 (24645 hom., cov: 32)
• Consequence: ITGB2 NM_001127491.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.147

Genes affected

ITGB2-AS1 (HGNC:):

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGB2	NM_001127491.3	c.-4+4143T>C		intron_variant			NP_001120963.2
ITGB2-AS1	NR_038311.1	n.388+1528A>G		intron_variant
ITGB2-AS1	NR_038312.1	n.388+1528A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGB2-AS1	ENST00000441379.5	n.278-2357A>G		intron_variant		1
ITGB2	ENST00000355153.8	c.-4+4143T>C		intron_variant		2		ENSP00000347279.4
ITGB2	ENST00000397850.6	c.-233-3461T>C		intron_variant		5		ENSP00000380948.2

Frequencies

GnomAD3 genomes AF: 0.550 AC: 83531 AN: 151932 Hom.: 24595 Cov.: 32

Gnomad AFR AF: 0.770

Gnomad AMI AF: 0.582

Gnomad AMR AF: 0.552

Gnomad ASJ AF: 0.495

Gnomad EAS AF: 0.432

Gnomad SAS AF: 0.391

Gnomad FIN AF: 0.438

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.526

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

GnomAD4 genome AF: 0.550 AC: 83651 AN: 152050 Hom.: 24645 Cov.: 32 AF XY: 0.546 AC XY: 40591 AN XY: 74320

Gnomad4 AFR AF: 0.770

Gnomad4 AMR AF: 0.553

Gnomad4 ASJ AF: 0.495

Gnomad4 EAS AF: 0.434

Gnomad4 SAS AF: 0.391

Gnomad4 FIN AF: 0.438

Gnomad4 NFE AF: 0.456

Gnomad4 OTH AF: 0.527

Alfa AF: 0.476 Hom.: 36906

Bravo AF: 0.576

Asia WGS AF: 0.447 AC: 1558 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	2.3
DANN	Benign	0.38

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2838738; hg19: chr21-46344426;