rs1041457

Variant names:

• chr21-44901903-A-G
• rs1041457
• NM_000211.5:c.500-170T>C

Your query was ambiguous. Multiple possible variants found:

• chr21-44901903-A-G
• chr21-44901903-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000211.5(ITGB2):​c.500-170T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 710,714 control chromosomes in the GnomAD database, including 43,650 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.37 (11001 hom., cov: 34)
  • Exomes 𝑓: 0.33 (32649 hom.)
• Consequence: ITGB2 NM_000211.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.03
• Publications: 6 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, Orphanet, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BP6: Variant 21-44901903-A-G is Benign according to our data. Variant chr21-44901903-A-G is described in ClinVar as Benign. ClinVar VariationId is 1276148.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.424 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB2	NM_000211.5	MANE Select	c.500-170T>C		intron	N/A	NP_000202.3
	ITGB2	NM_001127491.3		c.500-170T>C		intron	N/A	NP_001120963.2
	ITGB2	NM_001303238.2		c.293-170T>C		intron	N/A	NP_001290167.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB2	ENST00000652462.1	MANE Select	c.500-170T>C		intron	N/A	ENSP00000498780.1
	ITGB2	ENST00000302347.10	TSL:1	c.500-170T>C		intron	N/A	ENSP00000303242.6
	ITGB2	ENST00000397852.5	TSL:1	c.500-170T>C		intron	N/A	ENSP00000380950.1

Frequencies

GnomAD3 genomes AF: 0.374 AC: 56887 AN: 151938 Hom.: 10991 Cov.: 34

Gnomad AFR AF: 0.429

Gnomad AMI AF: 0.520

Gnomad AMR AF: 0.397

Gnomad ASJ AF: 0.435

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.361

Gnomad OTH AF: 0.362

GnomAD4 exome AF: 0.332 AC: 185369 AN: 558658 Hom.: 32649 AF XY: 0.329 AC XY: 94834 AN XY: 288070

African (AFR) AF: 0.432 AC: 6264 AN: 14498

American (AMR) AF: 0.375 AC: 7155 AN: 19104

Ashkenazi Jewish (ASJ) AF: 0.433 AC: 6187 AN: 14284

East Asian (EAS) AF: 0.155 AC: 4886 AN: 31488

South Asian (SAS) AF: 0.259 AC: 12430 AN: 48036

European-Finnish (FIN) AF: 0.341 AC: 10118 AN: 29686

Middle Eastern (MID) AF: 0.412 AC: 948 AN: 2300

European-Non Finnish (NFE) AF: 0.343 AC: 126902 AN: 369674

Other (OTH) AF: 0.354 AC: 10479 AN: 29588

GnomAD4 genome AF: 0.374 AC: 56933 AN: 152056 Hom.: 11001 Cov.: 34 AF XY: 0.370 AC XY: 27522 AN XY: 74318

African (AFR) AF: 0.429 AC: 17804 AN: 41468

American (AMR) AF: 0.397 AC: 6066 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.435 AC: 1509 AN: 3468

East Asian (EAS) AF: 0.184 AC: 953 AN: 5166

South Asian (SAS) AF: 0.241 AC: 1163 AN: 4820

European-Finnish (FIN) AF: 0.337 AC: 3566 AN: 10576

Middle Eastern (MID) AF: 0.425 AC: 124 AN: 292

European-Non Finnish (NFE) AF: 0.361 AC: 24518 AN: 67946

Other (OTH) AF: 0.358 AC: 756 AN: 2112

Alfa AF: 0.370 Hom.: 11136

Bravo AF: 0.383

Asia WGS AF: 0.231 AC: 807 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

May 12, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.52
DANN	Benign	0.39
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

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: rs1041457; hg19: chr21-46321818; COSMIC: COSV56609896; COSMIC: COSV56609896;