21-44921282-T-C

Variant names:

• chr21-44921282-T-C
• rs2070946
• ENST00000441379.5:n.232T>C

Variant summary

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

The NM_001127491.3(ITGB2):​c.-4+7372A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 152,208 control chromosomes in the GnomAD database, including 4,073 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 0.23 (4070 hom., cov: 32)
  • Exomes 𝑓: 0.17 (3 hom.)
• Consequence: ITGB2 NM_001127491.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.27

Genes affected

ITGB2-AS1 (HGNC:44304): (ITGB2 antisense RNA 1)

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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGB2	NM_001127491.3	c.-4+7372A>G		intron_variant	Intron 1 of 15		NP_001120963.2
ITGB2-AS1	NR_038311.1	n.248T>C		non_coding_transcript_exon_variant	Exon 1 of 5
ITGB2-AS1	NR_038312.1	n.248T>C		non_coding_transcript_exon_variant	Exon 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGB2-AS1	ENST00000441379.5	n.232T>C		non_coding_transcript_exon_variant	Exon 1 of 4	1
ITGB2	ENST00000355153.8	c.-4+7372A>G		intron_variant	Intron 1 of 15	2		ENSP00000347279.4
ITGB2	ENST00000397850.6	c.-233-232A>G		intron_variant	Intron 1 of 16	5		ENSP00000380948.2

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34461 AN: 151924 Hom.: 4058 Cov.: 32

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.266

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.232

GnomAD4 exome AF: 0.169 AC: 28 AN: 166 Hom.: 3 Cov.: 0 AF XY: 0.190 AC XY: 22 AN XY: 116

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.500

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.300

Gnomad4 FIN exome AF: 0.167

Gnomad4 NFE exome AF: 0.151

Gnomad4 OTH exome AF: 0.208

GnomAD4 genome AF: 0.227 AC: 34512 AN: 152042 Hom.: 4070 Cov.: 32 AF XY: 0.227 AC XY: 16840 AN XY: 74332

Gnomad4 AFR AF: 0.202

Gnomad4 AMR AF: 0.299

Gnomad4 ASJ AF: 0.266

Gnomad4 EAS AF: 0.105

Gnomad4 SAS AF: 0.306

Gnomad4 FIN AF: 0.175

Gnomad4 NFE AF: 0.234

Gnomad4 OTH AF: 0.235

Alfa AF: 0.226 Hom.: 4318

Bravo AF: 0.235

Asia WGS AF: 0.214 AC: 745 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.44
DANN	Benign	0.42

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2070946; hg19: chr21-46341197;