rs375146934

Variant names:

• chr21-44886247-G-A
• rs375146934
• NM_000211.5:c.*121C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_000211.5(ITGB2):​c.*121C>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 0.00345 in 1,025,512 control chromosomes in the GnomAD database, including 114 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0015 (9 hom., cov: 33)
  • Exomes 𝑓: 0.0038 (105 hom.)
• Consequence: ITGB2 NM_000211.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.189
• 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: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, Ambry Genetics, Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 21-44886247-G-A is Benign according to our data. Variant chr21-44886247-G-A is described in ClinVar as Benign. ClinVar VariationId is 340135.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00153 (233/152180) while in subpopulation SAS AF = 0.0398 (192/4820). AF 95% confidence interval is 0.0352. There are 9 homozygotes in GnomAd4. There are 162 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 9 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.*121C>T		3_prime_UTR	Exon 16 of 16	NP_000202.3	P05107
	ITGB2	NM_001127491.3		c.*121C>T		3_prime_UTR	Exon 16 of 16	NP_001120963.2	P05107
	ITGB2	NM_001303238.2		c.*121C>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.*121C>T		3_prime_UTR	Exon 16 of 16	ENSP00000498780.1	A0A494C0X7
	ITGB2	ENST00000302347.10	TSL:1	c.*121C>T		3_prime_UTR	Exon 17 of 17	ENSP00000303242.6	A0AAA9WZN5
	ITGB2	ENST00000397852.5	TSL:1	c.*121C>T		3_prime_UTR	Exon 15 of 15	ENSP00000380950.1	P05107

Frequencies

GnomAD3 genomes AF: 0.00154 AC: 234 AN: 152062 Hom.: 9 Cov.: 33

Gnomad AFR AF: 0.000556

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000328

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00174

Gnomad SAS AF: 0.0400

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000959

GnomAD4 exome AF: 0.00379 AC: 3307 AN: 873332 Hom.: 105 Cov.: 12 AF XY: 0.00545 AC XY: 2481 AN XY: 455354

African (AFR) AF: 0.000316 AC: 7 AN: 22132

American (AMR) AF: 0.000142 AC: 6 AN: 42286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22200

East Asian (EAS) AF: 0.000191 AC: 7 AN: 36606

South Asian (SAS) AF: 0.0422 AC: 3105 AN: 73506

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51306

Middle Eastern (MID) AF: 0.00336 AC: 11 AN: 3276

European-Non Finnish (NFE) AF: 0.000117 AC: 68 AN: 581182

Other (OTH) AF: 0.00252 AC: 103 AN: 40838

GnomAD4 genome AF: 0.00153 AC: 233 AN: 152180 Hom.: 9 Cov.: 33 AF XY: 0.00218 AC XY: 162 AN XY: 74382

African (AFR) AF: 0.000554 AC: 23 AN: 41524

American (AMR) AF: 0.000327 AC: 5 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5168

South Asian (SAS) AF: 0.0398 AC: 192 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67998

Other (OTH) AF: 0.000949 AC: 2 AN: 2108

Alfa AF: 0.000208 Hom.: 0

Bravo AF: 0.000465

Asia WGS AF: 0.0220 AC: 77 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Leukocyte adhesion deficiency 1 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.3
DANN	Benign	0.56
PhyloP100		-0.19
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: rs375146934; hg19: chr21-46306162;