20-1682353-G-T

Variant names:

• chr20-1682353-G-T
• rs202548
• ENST00000340424.4:n.461-11156C>A

Variant summary

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

The ENST00000340424.4(SIRPB3P):​n.461-11156C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.808 in 152,132 control chromosomes in the GnomAD database, including 49,911 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.81 (49911 hom., cov: 32)
• Consequence: SIRPB3P ENST00000340424.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.926
• Publications: 4 publications found

Genes affected

SIRPB3P (HGNC:49209): (signal regulatory protein beta 3, pseudogene)

ENSG00000296776 (HGNC:):

SIRPG (HGNC:15757): (signal regulatory protein gamma) 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. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

SIRPG Gene-Disease associations (from GenCC):

• male infertility with azoospermia or oligozoospermia due to single gene mutation

  Inheritance: AR Classification: LIMITED Submitted by: King Faisal Specialist Hospital and Research Center

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIRPG	XM_011529286.3	c.-27+3979C>A		intron_variant	Intron 1 of 5		XP_011527588.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIRPB3P	ENST00000340424.4	n.461-11156C>A		intron_variant	Intron 2 of 4	6
ENSG00000296776	ENST00000741926.1	n.135+3979C>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.808 AC: 122857 AN: 152014 Hom.: 49891 Cov.: 32

Gnomad AFR AF: 0.733

Gnomad AMI AF: 0.871

Gnomad AMR AF: 0.847

Gnomad ASJ AF: 0.791

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.901

Gnomad FIN AF: 0.768

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.830

Gnomad OTH AF: 0.812

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.808 AC: 122932 AN: 152132 Hom.: 49911 Cov.: 32 AF XY: 0.809 AC XY: 60145 AN XY: 74380

African (AFR) AF: 0.733 AC: 30392 AN: 41474

American (AMR) AF: 0.847 AC: 12948 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.791 AC: 2744 AN: 3470

East Asian (EAS) AF: 1.00 AC: 5174 AN: 5176

South Asian (SAS) AF: 0.900 AC: 4348 AN: 4830

European-Finnish (FIN) AF: 0.768 AC: 8123 AN: 10582

Middle Eastern (MID) AF: 0.806 AC: 237 AN: 294

European-Non Finnish (NFE) AF: 0.830 AC: 56462 AN: 67992

Other (OTH) AF: 0.810 AC: 1710 AN: 2110

Alfa AF: 0.819 Hom.: 105216

Bravo AF: 0.811

Asia WGS AF: 0.940 AC: 3267 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.81
DANN	Benign	0.22
PhyloP100		-0.93

Splicing

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

Other links and lift over

dbSNP: rs202548; hg19: chr20-1662999;