20-1578340-C-T

Variant names:

• chr20-1578340-C-T
• rs201638914
• NM_006065.5:c.431G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_006065.5(SIRPB1):​c.431G>A​(p.Arg144His) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000236 in 1,583,202 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00024 (2 hom., cov: 29)
  • Exomes 𝑓: 0.00024 (26 hom.)
• Consequence: SIRPB1 NM_006065.5 missense, splice_region
• Scores: Splicing: ADA: 0.00005694
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.459
• 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009126037).
• BS2: High Homozygotes in GnomAd4 at 2 gene

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.431G>A	p.Arg144His	missense splice_region	Exon 2 of 6	NP_006056.2	O00241-1
	SIRPB1	NM_001083910.4		c.431G>A	p.Arg144His	missense splice_region	Exon 2 of 4	NP_001077379.1	O00241-2
	SIRPB1	NM_001330639.2		c.428G>A	p.Arg143His	missense splice_region	Exon 2 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.431G>A	p.Arg144His	missense splice_region	Exon 2 of 6	ENSP00000371018.5	O00241-1
	SIRPB1	ENST00000381603.7	TSL:1	c.431G>A	p.Arg144His	missense splice_region	Exon 2 of 4	ENSP00000371016.3	O00241-2
	ENSG00000260861	ENST00000564763.1	TSL:4	c.431G>A	p.Arg144His	missense splice_region	Exon 2 of 3	ENSP00000457944.1	H3BV43

Frequencies

GnomAD3 genomes AF: 0.000237 AC: 35 AN: 147392 Hom.: 2 Cov.: 29

Gnomad AFR AF: 0.0000246

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000675

Gnomad ASJ AF: 0.00586

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000848

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000106

Gnomad OTH AF: 0.000502

GnomAD2 exomes AF: 0.000380 AC: 94 AN: 247406 AF XY: 0.000381

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00574

Gnomad EAS exome AF: 0.000598

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000718

Gnomad OTH exome AF: 0.000667

GnomAD4 exome AF: 0.000235 AC: 338 AN: 1435692 Hom.: 26 Cov.: 31 AF XY: 0.000237 AC XY: 169 AN XY: 714550

African (AFR) AF: 0.0000601 AC: 2 AN: 33268

American (AMR) AF: 0.0000450 AC: 2 AN: 44478

Ashkenazi Jewish (ASJ) AF: 0.00641 AC: 165 AN: 25734

East Asian (EAS) AF: 0.000302 AC: 12 AN: 39700

South Asian (SAS) AF: 0.000583 AC: 50 AN: 85774

European-Finnish (FIN) AF: 0.0000196 AC: 1 AN: 50990

Middle Eastern (MID) AF: 0.000357 AC: 2 AN: 5596

European-Non Finnish (NFE) AF: 0.0000633 AC: 69 AN: 1090768

Other (OTH) AF: 0.000589 AC: 35 AN: 59384

GnomAD4 genome AF: 0.000237 AC: 35 AN: 147510 Hom.: 2 Cov.: 29 AF XY: 0.000181 AC XY: 13 AN XY: 71718

African (AFR) AF: 0.0000245 AC: 1 AN: 40748

American (AMR) AF: 0.0000674 AC: 1 AN: 14838

Ashkenazi Jewish (ASJ) AF: 0.00586 AC: 20 AN: 3412

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5158

South Asian (SAS) AF: 0.000849 AC: 4 AN: 4712

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 286

European-Non Finnish (NFE) AF: 0.000106 AC: 7 AN: 66032

Other (OTH) AF: 0.000496 AC: 1 AN: 2016

Alfa AF: 0.000616 Hom.: 5

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000472 AC: 4

ExAC AF: 0.000366 AC: 44

Asia WGS AF: 0.000289 AC: 1 AN: 3468

EpiCase AF: 0.000278

EpiControl AF: 0.0000602

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	12
DANN	Benign	0.91
DEOGEN2	Benign	0.0088	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0077	N
LIST_S2	Benign	0.26	T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.0079	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.1	L
PhyloP100		-0.46
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.87	N
REVEL	Benign	0.016
Sift	Benign	0.65	T
Sift4G	Benign	0.57	T
Polyphen		0.19	B
Vest4		0.088
MVP		0.030
MPC		0.16
ClinPred		0.0047	T
GERP RS		-1.2
Varity_R		0.10
gMVP		0.28
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000057
dbscSNV1_RF	Benign	0.0020
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: rs201638914; hg19: chr20-1558986; COSMIC: COSV99498273;