rs2243603

Variant names:

• chr20-1566265-C-G
• rs2243603
• NM_006065.5:c.1087G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006065.5(SIRPB1):​c.1087G>C​(p.Ala363Pro) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.773 in 1,591,648 control chromosomes in the GnomAD database, including 477,469 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.80 (49363 hom., cov: 31)
  • Exomes 𝑓: 0.77 (428106 hom.)
• Consequence: SIRPB1 NM_006065.5 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.156
• Publications: 39 publications found

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]

ENSG00000260861 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=9.500686E-7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.902 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006065.5. 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
	SIRPB1	NM_006065.5	MANE Select	c.1087G>C	p.Ala363Pro	missense splice_region	Exon 5 of 6	NP_006056.2	O00241-1
	SIRPB1	NM_001083910.4		c.436G>C	p.Ala146Pro	missense splice_region	Exon 3 of 4	NP_001077379.1	O00241-2
	SIRPB1	NM_001330639.2		c.433G>C	p.Ala145Pro	missense splice_region	Exon 3 of 4	NP_001317568.1	H9KV29

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIRPB1	ENST00000381605.9	TSL:1 MANE Select	c.1087G>C	p.Ala363Pro	missense splice_region	Exon 5 of 6	ENSP00000371018.5	O00241-1
	SIRPB1	ENST00000381603.7	TSL:1	c.436G>C	p.Ala146Pro	missense splice_region	Exon 3 of 4	ENSP00000371016.3	O00241-2
	ENSG00000260861	ENST00000564763.1	TSL:4	c.433+12073G>C		intron	N/A	ENSP00000457944.1	H3BV43

Frequencies

GnomAD3 genomes AF: 0.802 AC: 121868 AN: 152028 Hom.: 49314 Cov.: 31

Gnomad AFR AF: 0.910

Gnomad AMI AF: 0.741

Gnomad AMR AF: 0.679

Gnomad ASJ AF: 0.740

Gnomad EAS AF: 0.800

Gnomad SAS AF: 0.760

Gnomad FIN AF: 0.801

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.771

Gnomad OTH AF: 0.785

GnomAD2 exomes AF: 0.772 AC: 168748 AN: 218702 AF XY: 0.774

Gnomad AFR exome AF: 0.915

Gnomad AMR exome AF: 0.626

Gnomad ASJ exome AF: 0.744

Gnomad EAS exome AF: 0.821

Gnomad FIN exome AF: 0.797

Gnomad NFE exome AF: 0.784

Gnomad OTH exome AF: 0.773

GnomAD4 exome AF: 0.770 AC: 1108839 AN: 1439502 Hom.: 428106 Cov.: 29 AF XY: 0.771 AC XY: 550473 AN XY: 714392

African (AFR) AF: 0.918 AC: 30554 AN: 33300

American (AMR) AF: 0.631 AC: 25579 AN: 40538

Ashkenazi Jewish (ASJ) AF: 0.735 AC: 18826 AN: 25620

East Asian (EAS) AF: 0.788 AC: 30841 AN: 39156

South Asian (SAS) AF: 0.762 AC: 63336 AN: 83132

European-Finnish (FIN) AF: 0.794 AC: 41208 AN: 51918

Middle Eastern (MID) AF: 0.813 AC: 4659 AN: 5734

European-Non Finnish (NFE) AF: 0.770 AC: 847278 AN: 1100536

Other (OTH) AF: 0.782 AC: 46558 AN: 59568

GnomAD4 genome AF: 0.802 AC: 121967 AN: 152146 Hom.: 49363 Cov.: 31 AF XY: 0.799 AC XY: 59395 AN XY: 74354

African (AFR) AF: 0.910 AC: 37778 AN: 41526

American (AMR) AF: 0.678 AC: 10369 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.740 AC: 2567 AN: 3470

East Asian (EAS) AF: 0.800 AC: 4125 AN: 5154

South Asian (SAS) AF: 0.759 AC: 3659 AN: 4820

European-Finnish (FIN) AF: 0.801 AC: 8474 AN: 10580

Middle Eastern (MID) AF: 0.857 AC: 252 AN: 294

European-Non Finnish (NFE) AF: 0.771 AC: 52409 AN: 67990

Other (OTH) AF: 0.787 AC: 1660 AN: 2110

Alfa AF: 0.777 Hom.: 33913

Bravo AF: 0.799

TwinsUK AF: 0.767 AC: 2845

ALSPAC AF: 0.763 AC: 2939

ESP6500AA AF: 0.903 AC: 3979

ESP6500EA AF: 0.773 AC: 6645

ExAC AF: 0.762 AC: 91819

Asia WGS AF: 0.801 AC: 2785 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	2.7
DANN	Benign	0.54
DEOGEN2	Benign	0.0030	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.00013	N
LIST_S2	Benign	0.33	T
MetaRNN	Benign	9.1e-7	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-1.8	N
PhyloP100		-0.16
PrimateAI	Benign	0.20	T
PROVEAN	Benign	0.27	N
REVEL	Benign	0.025
Sift	Benign	0.28	T
Sift4G	Benign	0.28	T
Polyphen		0.0	B
Vest4		0.10
MPC		0.17
ClinPred		0.0027	T
GERP RS		-3.1
Varity_R		0.17
gMVP		0.17
Mutation Taster		=99/1	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: rs2243603; hg19: chr20-1546911; COSMIC: COSV53538817; COSMIC: COSV53538817;