rs4818986

Positions:

• chr21-44927430-C-T

Variant summary

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

The NM_001127491.3(ITGB2):​c.-4+1224G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 151,832 control chromosomes in the GnomAD database, including 4,711 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 0.24 (4711 hom., cov: 31)
• Consequence: ITGB2 NM_001127491.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.276

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGB2	NM_001127491.3	c.-4+1224G>A		intron_variant			NP_001120963.2
ITGB2-AS1	NR_038311.1	n.526-195C>T		intron_variant
ITGB2-AS1	NR_038312.1	n.526-424C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGB2-AS1	ENST00000441379.5	n.415-195C>T		intron_variant		1
ITGB2	ENST00000355153.8	c.-4+1224G>A		intron_variant		2		ENSP00000347279.4
ITGB2	ENST00000397850.6	c.-234+1224G>A		intron_variant		5		ENSP00000380948.2

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37117 AN: 151714 Hom.: 4697 Cov.: 31

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.304

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.242

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

GnomAD4 genome AF: 0.245 AC: 37181 AN: 151832 Hom.: 4711 Cov.: 31 AF XY: 0.244 AC XY: 18092 AN XY: 74206

Gnomad4 AFR AF: 0.256

Gnomad4 AMR AF: 0.304

Gnomad4 ASJ AF: 0.273

Gnomad4 EAS AF: 0.105

Gnomad4 SAS AF: 0.296

Gnomad4 FIN AF: 0.191

Gnomad4 NFE AF: 0.238

Gnomad4 OTH AF: 0.244

Alfa AF: 0.238 Hom.: 550

Bravo AF: 0.255

Asia WGS AF: 0.214 AC: 743 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.8
DANN	Benign	0.91

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4818986; hg19: chr21-46347345;