20-1578387-A-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_006065.5(SIRPB1):c.384T>C(p.Pro128=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000964 in 1,587,154 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 29)
  • Exomes 𝑓: 0.000094 (13 hom.)
• Consequence: SIRPB1 NM_006065.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.04

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]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BP6: Variant 20-1578387-A-G is Benign according to our data. Variant chr20-1578387-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2652135.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.04 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIRPB1	NM_006065.5	c.384T>C	p.Pro128=	synonymous_variant	2/6	ENST00000381605.9
SIRPB1	NM_001083910.4	c.384T>C	p.Pro128=	synonymous_variant	2/4
SIRPB1	NM_001330639.2	c.381T>C	p.Pro127=	synonymous_variant	2/4
SIRPB1	XM_005260641.4	c.381T>C	p.Pro127=	synonymous_variant	2/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIRPB1	ENST00000381605.9	c.384T>C	p.Pro128=	synonymous_variant	2/6	1	NM_006065.5

Frequencies

GnomAD3 genomes AF: 0.000122 AC: 18 AN: 147336 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.000172

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000270

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000909

Gnomad OTH AF: 0.000504

GnomAD3 exomes AF: 0.000105 AC: 26 AN: 247542 Hom.: 3 AF XY: 0.0000747 AC XY: 10 AN XY: 133784

Gnomad AFR exome AF: 0.000371

Gnomad AMR exome AF: 0.000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.0000328

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000628

Gnomad OTH exome AF: 0.000167

GnomAD4 exome AF: 0.0000938 AC: 135 AN: 1439706 Hom.: 13 Cov.: 31 AF XY: 0.0000851 AC XY: 61 AN XY: 716474

Gnomad4 AFR exome AF: 0.000391

Gnomad4 AMR exome AF: 0.000360

Gnomad4 ASJ exome AF: 0.0000776

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000233

Gnomad4 FIN exome AF: 0.0000391

Gnomad4 NFE exome AF: 0.0000832

Gnomad4 OTH exome AF: 0.000118

GnomAD4 genome AF: 0.000122 AC: 18 AN: 147448 Hom.: 0 Cov.: 29 AF XY: 0.0000976 AC XY: 7 AN XY: 71720

Gnomad4 AFR AF: 0.000172

Gnomad4 AMR AF: 0.000269

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000909

Gnomad4 OTH AF: 0.000499

Alfa AF: 0.0000857 Hom.: 0

Bravo AF: 0.000166

Asia WGS AF: 0.000289 AC: 1 AN: 3468

EpiCase AF: 0.000111

EpiControl AF: 0.000120

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2022

SIRPB1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.78
Dann	Benign	0.41

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

Other links and lift over

dbSNP: rs142333512; hg19: chr20-1559033;