Genetic Variant SIRPB2:p.Ala293Thr (chr20-1476319-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001122962.2(SIRPB2):c.877G>A(p.Ala293Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000198 in 1,612,150 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00020 ( 0 hom. )

Consequence

SIRPB2
NM_001122962.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0750

Publications

3 publications found

Variant links:

Genes affected

SIRPB2 (HGNC:16247): (signal regulatory protein beta 2) Predicted to be integral component of membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SIRPB2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.020780534).

BP6

Variant 20-1476319-C-T is Benign according to our data. Variant chr20-1476319-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3162482.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001122962.2. 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
	SIRPB2	NM_001122962.2	MANE Select	c.877G>A	p.Ala293Thr	missense	Exon 5 of 5	NP_001116434.1	Q5JXA9-1
	SIRPB2	NM_001134836.2		c.583G>A	p.Ala195Thr	missense	Exon 5 of 5	NP_001128308.1	Q5JXA9-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SIRPB2	ENST00000359801.8	TSL:2 MANE Select	c.877G>A	p.Ala293Thr	missense	Exon 5 of 5	ENSP00000352849.3	Q5JXA9-1
SIRPB2	ENST00000444444.2	TSL:2	c.583G>A	p.Ala195Thr	missense	Exon 5 of 5	ENSP00000402438.1	Q5JXA9-3
SIRPB2	ENST00000965661.1		c.535G>A	p.Ala179Thr	missense	Exon 4 of 4	ENSP00000635720.1

Frequencies

GnomAD3 genomes

AF:

0.000217

AC:

AN:

151758

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000727

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000236

Gnomad OTH

AF:

0.00144

GnomAD2 exomes

AF:

0.000170

AC:

AN:

247374

AF XY:

0.000171

show subpopulations

Gnomad AFR exome

AF:

0.0000649

Gnomad AMR exome

AF:

0.000381

Gnomad ASJ exome

AF:

0.000101

Gnomad EAS exome

AF:

0.0000559

Gnomad FIN exome

AF:

0.0000465

Gnomad NFE exome

AF:

0.000206

Gnomad OTH exome

AF:

0.000167

GnomAD4 exome

AF:

0.000196

AC:

286

AN:

1460392

Hom.:

Cov.:

AF XY:

0.000208

AC XY:

151

AN XY:

726546

show subpopulations

African (AFR)

AF:

0.0000599

AC:

AN:

33402

American (AMR)

AF:

0.000428

AC:

AN:

44414

Ashkenazi Jewish (ASJ)

AF:

0.0000384

AC:

AN:

26064

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39686

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86174

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53396

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5388

European-Non Finnish (NFE)

AF:

0.000208

AC:

231

AN:

1111588

Other (OTH)

AF:

0.000481

AC:

AN:

60280

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000217

AC:

AN:

151758

Hom.:

Cov.:

AF XY:

0.000229

AC XY:

AN XY:

74074

show subpopulations

African (AFR)

AF:

0.0000727

AC:

AN:

41268

American (AMR)

AF:

0.000589

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.000577

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5150

South Asian (SAS)

AF:

0.00

AC:

AN:

4798

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10578

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000236

AC:

AN:

67918

Other (OTH)

AF:

0.00144

AC:

AN:

2082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000185

Hom.:

Bravo

AF:

0.000261

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000419

AC:

ExAC

AF:

0.000133

AC:

EpiCase

AF:

0.000382

EpiControl

AF:

0.000593

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.38

(source)

DANN

Benign

0.76

DEOGEN2

Benign

0.0014

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0013

LIST_S2

Benign

0.37

M_CAP

Benign

0.0017

MetaRNN

Benign

0.021

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-1.0

PhyloP100

0.075

PrimateAI

Benign

0.29

PROVEAN

Benign

0.25

REVEL

Benign

0.019

Sift

Benign

0.91

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.044

MVP

0.048

MPC

0.046

ClinPred

0.0029

GERP RS

-5.6

Varity_R

0.028

gMVP

0.13

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over