NM_000211.5:c.*167C>T

Variant names:

• chr21-44886201-G-A
• rs561251271
• NM_000211.5:c.*167C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_000211.5(ITGB2):​c.*167C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00543 in 689,398 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0043 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0057 (16 hom.)
• Consequence: ITGB2 NM_000211.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0970
• Publications: 0 publications found

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]

ITGB2 Gene-Disease associations (from GenCC):

• leukocyte adhesion deficiency 1

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 21-44886201-G-A is Benign according to our data. Variant chr21-44886201-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 340131.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00431 (656/152136) while in subpopulation NFE AF = 0.00722 (491/67992). AF 95% confidence interval is 0.00669. There are 2 homozygotes in GnomAd4. There are 304 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000211.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB2	NM_000211.5	MANE Select	c.*167C>T		3_prime_UTR	Exon 16 of 16	NP_000202.3	P05107
	ITGB2	NM_001127491.3		c.*167C>T		3_prime_UTR	Exon 16 of 16	NP_001120963.2	P05107
	ITGB2	NM_001303238.2		c.*167C>T		3_prime_UTR	Exon 16 of 16	NP_001290167.1	B4E0R1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB2	ENST00000652462.1	MANE Select	c.*167C>T		3_prime_UTR	Exon 16 of 16	ENSP00000498780.1	A0A494C0X7
	ITGB2	ENST00000302347.10	TSL:1	c.*167C>T		3_prime_UTR	Exon 17 of 17	ENSP00000303242.6	A0AAA9WZN5
	ITGB2	ENST00000397852.5	TSL:1	c.*167C>T		3_prime_UTR	Exon 15 of 15	ENSP00000380950.1	P05107

Frequencies

GnomAD3 genomes AF: 0.00432 AC: 656 AN: 152018 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00118

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00308

Gnomad ASJ AF: 0.00634

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000830

Gnomad FIN AF: 0.00330

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00722

Gnomad OTH AF: 0.00383

GnomAD4 exome AF: 0.00575 AC: 3089 AN: 537262 Hom.: 16 Cov.: 6 AF XY: 0.00548 AC XY: 1575 AN XY: 287276

African (AFR) AF: 0.00102 AC: 16 AN: 15626

American (AMR) AF: 0.00252 AC: 83 AN: 32930

Ashkenazi Jewish (ASJ) AF: 0.00745 AC: 132 AN: 17712

East Asian (EAS) AF: 0.00 AC: 0 AN: 31746

South Asian (SAS) AF: 0.00121 AC: 70 AN: 57966

European-Finnish (FIN) AF: 0.00407 AC: 152 AN: 37346

Middle Eastern (MID) AF: 0.000435 AC: 1 AN: 2298

European-Non Finnish (NFE) AF: 0.00794 AC: 2481 AN: 312294

Other (OTH) AF: 0.00525 AC: 154 AN: 29344

GnomAD4 genome AF: 0.00431 AC: 656 AN: 152136 Hom.: 2 Cov.: 33 AF XY: 0.00409 AC XY: 304 AN XY: 74370

African (AFR) AF: 0.00118 AC: 49 AN: 41498

American (AMR) AF: 0.00308 AC: 47 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00634 AC: 22 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000831 AC: 4 AN: 4814

European-Finnish (FIN) AF: 0.00330 AC: 35 AN: 10594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00722 AC: 491 AN: 67992

Other (OTH) AF: 0.00379 AC: 8 AN: 2112

Alfa AF: 0.00630 Hom.: 2

Bravo AF: 0.00404

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Leukocyte adhesion deficiency 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.2
DANN	Benign	0.52
PhyloP100		0.097
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs561251271; hg19: chr21-46306116;