20-1571035-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_006065.5(SIRPB1):​c.854C>T​(p.Thr285Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

SIRPB1
NM_006065.5 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.573
Variant links:
Genes affected
SIRPB1 (HGNC:15928): (signal regulatory protein beta 1) The protein encoded by this gene is a member of the signal-regulatory-protein (SIRP) family, and also belongs to the immunoglobulin superfamily. SIRP family members are receptor-type transmembrane glycoproteins known to be involved in the negative regulation of receptor tyrosine kinase-coupled signaling processes. This protein was found to interact with TYROBP/DAP12, a protein bearing immunoreceptor tyrosine-based activation motifs. This protein was also reported to participate in the recruitment of tyrosine kinase SYK. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2009]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3137759).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SIRPB1NM_006065.5 linkuse as main transcriptc.854C>T p.Thr285Ile missense_variant 4/6 ENST00000381605.9
SIRPB1XM_005260641.4 linkuse as main transcriptc.851C>T p.Thr284Ile missense_variant 4/6
SIRPB1NM_001083910.4 linkuse as main transcriptc.434-4768C>T intron_variant
SIRPB1NM_001330639.2 linkuse as main transcriptc.431-4768C>T intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SIRPB1ENST00000381605.9 linkuse as main transcriptc.854C>T p.Thr285Ile missense_variant 4/61 NM_006065.5 O00241-1

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
1
AN:
152178
Hom.:
0
Cov.:
32
FAILED QC
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000358
AC:
9
AN:
251410
Hom.:
0
AF XY:
0.0000515
AC XY:
7
AN XY:
135868
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000261
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000130
AC:
19
AN:
1461876
Hom.:
0
Cov.:
34
AF XY:
0.0000193
AC XY:
14
AN XY:
727238
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000162
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000360
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1
ExAC
AF:
0.0000247
AC:
3

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMay 30, 2024The c.854C>T (p.T285I) alteration is located in exon 4 (coding exon 4) of the SIRPB1 gene. This alteration results from a C to T substitution at nucleotide position 854, causing the threonine (T) at amino acid position 285 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Benign
-0.41
T
BayesDel_noAF
Benign
-0.53
CADD
Benign
16
DANN
Uncertain
1.0
DEOGEN2
Benign
0.019
T;.
Eigen
Benign
0.056
Eigen_PC
Benign
-0.16
FATHMM_MKL
Benign
0.32
N
LIST_S2
Benign
0.80
T;T
M_CAP
Benign
0.0044
T
MetaRNN
Benign
0.31
T;T
MetaSVM
Benign
-1.2
T
MutationAssessor
Uncertain
2.2
M;.
MutationTaster
Benign
1.0
D;D;N
PrimateAI
Benign
0.39
T
PROVEAN
Uncertain
-4.1
D;D
REVEL
Benign
0.12
Sift
Benign
0.14
T;T
Sift4G
Benign
0.10
T;T
Polyphen
1.0
D;.
Vest4
0.38
MutPred
0.64
Gain of sheet (P = 0.0827);.;
MVP
0.14
MPC
0.61
ClinPred
0.67
D
GERP RS
1.4
Varity_R
0.14
gMVP
0.37

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs550434293; hg19: chr20-1551681; API