rs199948899

Variant names:

• chr21-44910275-G-A
• rs199948899
• NM_000211.5:c.147+9C>T

Your query was ambiguous. Multiple possible variants found:

• chr21-44910275-G-A
• chr21-44910275-G-C

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.147+9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00278 in 1,613,540 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0023 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0028 (7 hom.)
• Consequence: ITGB2 NM_000211.5 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 2.19
• 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

LOC107987303 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 21-44910275-G-A is Benign according to our data. Variant chr21-44910275-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 461470.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00231 (352/152284) while in subpopulation NFE AF = 0.00428 (291/68004). AF 95% confidence interval is 0.00388. There are 1 homozygotes in GnomAd4. There are 166 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 7 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.147+9C>T		intron	N/A	NP_000202.3	P05107
	ITGB2	NM_001127491.3		c.147+9C>T		intron	N/A	NP_001120963.2	P05107
	ITGB2	NM_001303238.2		c.-61+9C>T		intron	N/A	NP_001290167.1	B4E0R1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB2	ENST00000652462.1	MANE Select	c.147+9C>T		intron	N/A	ENSP00000498780.1	A0A494C0X7
	ITGB2	ENST00000302347.10	TSL:1	c.147+9C>T		intron	N/A	ENSP00000303242.6	A0AAA9WZN5
	ITGB2	ENST00000397852.5	TSL:1	c.147+9C>T		intron	N/A	ENSP00000380950.1	P05107

Frequencies

GnomAD3 genomes AF: 0.00231 AC: 352 AN: 152166 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000579

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00122

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00428

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.00201 AC: 500 AN: 249068 AF XY: 0.00210

Gnomad AFR exome AF: 0.000377

Gnomad AMR exome AF: 0.000901

Gnomad ASJ exome AF: 0.000300

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00122

Gnomad NFE exome AF: 0.00370

Gnomad OTH exome AF: 0.00165

GnomAD4 exome AF: 0.00282 AC: 4128 AN: 1461256 Hom.: 7 Cov.: 32 AF XY: 0.00272 AC XY: 1979 AN XY: 726898

African (AFR) AF: 0.000329 AC: 11 AN: 33466

American (AMR) AF: 0.00110 AC: 49 AN: 44668

Ashkenazi Jewish (ASJ) AF: 0.000613 AC: 16 AN: 26116

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.000290 AC: 25 AN: 86166

European-Finnish (FIN) AF: 0.00124 AC: 66 AN: 53278

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5726

European-Non Finnish (NFE) AF: 0.00342 AC: 3800 AN: 1111812

Other (OTH) AF: 0.00267 AC: 161 AN: 60342

GnomAD4 genome AF: 0.00231 AC: 352 AN: 152284 Hom.: 1 Cov.: 33 AF XY: 0.00223 AC XY: 166 AN XY: 74452

African (AFR) AF: 0.000578 AC: 24 AN: 41552

American (AMR) AF: 0.00105 AC: 16 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.000864 AC: 3 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4830

European-Finnish (FIN) AF: 0.00122 AC: 13 AN: 10620

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

European-Non Finnish (NFE) AF: 0.00428 AC: 291 AN: 68004

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.00323 Hom.: 1

Bravo AF: 0.00206

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00360

EpiControl AF: 0.00267

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Leukocyte adhesion deficiency 1 (3)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.55
DANN	Benign	0.78
PhyloP100		2.2
PromoterAI		0.052	Neutral
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: rs199948899; hg19: chr21-46330190;