20-1680043-G-T

Variant names:

• chr20-1680043-G-T
• rs1550266
• ENST00000340424.4:n.461-8846C>A

Variant summary

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

The ENST00000340424.4(SIRPB3P):​n.461-8846C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 152,110 control chromosomes in the GnomAD database, including 5,216 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 0.24 (5216 hom., cov: 32)
• Consequence: SIRPB3P ENST00000340424.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.926
• Publications: 3 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 = 0.57 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIRPG	XM_011529286.3	c.-27+6289C>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.461-8846C>A		intron_variant	Intron 2 of 4	6
ENSG00000296776	ENST00000741926.1	n.135+6289C>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36991 AN: 151992 Hom.: 5214 Cov.: 32

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.588

Gnomad SAS AF: 0.462

Gnomad FIN AF: 0.280

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.278

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

GnomAD4 genome AF: 0.243 AC: 37004 AN: 152110 Hom.: 5216 Cov.: 32 AF XY: 0.251 AC XY: 18636 AN XY: 74350

African (AFR) AF: 0.152 AC: 6292 AN: 41520

American (AMR) AF: 0.246 AC: 3756 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.320 AC: 1111 AN: 3470

East Asian (EAS) AF: 0.588 AC: 3034 AN: 5162

South Asian (SAS) AF: 0.461 AC: 2221 AN: 4818

European-Finnish (FIN) AF: 0.280 AC: 2955 AN: 10564

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.247 AC: 16800 AN: 67982

Other (OTH) AF: 0.282 AC: 595 AN: 2110

Alfa AF: 0.146 Hom.: 334

Bravo AF: 0.233

Asia WGS AF: 0.515 AC: 1791 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	0.95
DANN	Benign	0.16
PhyloP100		-0.93

Splicing

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

Other links and lift over

dbSNP: rs1550266; hg19: chr20-1660689;