rs140374707

Variant names:

• chr20-1571882-C-G
• rs140374707
• NM_006065.5:c.589G>C

Your query was ambiguous. Multiple possible variants found:

• chr20-1571882-C-G
• chr20-1571882-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006065.5(SIRPB1):​c.589G>C​(p.Val197Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V197M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SIRPB1 NM_006065.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.939
• Publications: 1 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18971169).

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.589G>C	p.Val197Leu	missense	Exon 3 of 6	NP_006056.2	O00241-1
	SIRPB1	NM_001083910.4		c.434-5615G>C		intron	N/A	NP_001077379.1	O00241-2
	SIRPB1	NM_001330639.2		c.431-5615G>C		intron	N/A	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.589G>C	p.Val197Leu	missense	Exon 3 of 6	ENSP00000371018.5	O00241-1
	SIRPB1	ENST00000381603.7	TSL:1	c.434-5615G>C		intron	N/A	ENSP00000371016.3	O00241-2
	ENSG00000260861	ENST00000564763.1	TSL:4	c.433+6456G>C		intron	N/A	ENSP00000457944.1	H3BV43

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461888 Hom.: 0 Cov.: 35 AF XY: 0.00000275 AC XY: 2 AN XY: 727246

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1112008

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	13
DANN	Benign	0.96
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
PhyloP100		-0.94
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.051
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0070	D
Polyphen		1.0	D
Vest4		0.21
MutPred		0.56		Gain of disorder (P = 0.193)
MVP		0.085
MPC		0.27
ClinPred		0.63	D
GERP RS		-2.3
PromoterAI		-0.00080	Neutral
Varity_R		0.30
gMVP		0.31
Mutation Taster		=99/1	polymorphism

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: rs140374707; hg19: chr20-1552528;