chr20-1578464-A-G

Position:

• chr20-1578464-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006065.5(SIRPB1):​c.307T>C​(p.Phe103Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000696 in 1,437,282 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: SIRPB1 NM_006065.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.08

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 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=0.41700476).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIRPB1	NM_006065.5	c.307T>C	p.Phe103Leu	missense_variant	2/6	ENST00000381605.9
SIRPB1	NM_001083910.4	c.307T>C	p.Phe103Leu	missense_variant	2/4
SIRPB1	NM_001330639.2	c.304T>C	p.Phe102Leu	missense_variant	2/4
SIRPB1	XM_005260641.4	c.304T>C	p.Phe102Leu	missense_variant	2/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIRPB1	ENST00000381605.9	c.307T>C	p.Phe103Leu	missense_variant	2/6	1	NM_006065.5

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 6.96e-7 AC: 1 AN: 1437282 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 715232

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.16e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 29

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 14, 2023

The c.307T>C (p.F103L) alteration is located in exon 2 (coding exon 2) of the SIRPB1 gene. This alteration results from a T to C substitution at nucleotide position 307, causing the phenylalanine (F) at amino acid position 103 to be replaced by a leucine (L). 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	Pathogenic	0.94
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	17
DANN	Benign	0.78
DEOGEN2	Benign	0.094	.;.;T;.;.;.
Eigen	Benign	-0.87
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.71	T;T;T;T;T;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.42	T;T;T;T;T;T
MetaSVM	Benign	-0.64	T
MutationAssessor	Pathogenic	3.4	.;.;M;M;.;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.39	T
PROVEAN	Pathogenic	-5.7	D;D;D;D;D;D
REVEL	Benign	0.18
Sift	Uncertain	0.017	D;D;D;D;D;D
Sift4G	Uncertain	0.015	D;D;D;D;D;D
Polyphen		0.095, 0.014	.;.;B;B;.;.
Vest4		0.26, 0.19, 0.32, 0.31
MutPred		0.74		.;Gain of disorder (P = 0.1441);Gain of disorder (P = 0.1441);Gain of disorder (P = 0.1441);.;.;
MVP		0.21
MPC		0.20
ClinPred		0.82	D
GERP RS		-0.12
Varity_R		0.54
gMVP		0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-1559110;