ENST00000340424.4:n.461-11696G>A

Variant names:

• chr20-1682893-C-T
• rs202546
• ENST00000340424.4:n.461-11696G>A

Variant summary

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

The ENST00000340424.4(SIRPB3P):​n.461-11696G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.509 in 152,068 control chromosomes in the GnomAD database, including 20,292 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 0.51 (20292 hom., cov: 33)
• Consequence: SIRPB3P ENST00000340424.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.942
• Publications: 7 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIRPG	XM_011529286.3	c.-27+3439G>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.461-11696G>A		intron_variant	Intron 2 of 4	6
ENSG00000296776	ENST00000741926.1	n.135+3439G>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.509 AC: 77319 AN: 151948 Hom.: 20281 Cov.: 33

Gnomad AFR AF: 0.386

Gnomad AMI AF: 0.731

Gnomad AMR AF: 0.586

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.419

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.488

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.582

Gnomad OTH AF: 0.496

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

GnomAD4 genome AF: 0.509 AC: 77357 AN: 152068 Hom.: 20292 Cov.: 33 AF XY: 0.503 AC XY: 37420 AN XY: 74362

African (AFR) AF: 0.386 AC: 15990 AN: 41456

American (AMR) AF: 0.586 AC: 8966 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.448 AC: 1552 AN: 3464

East Asian (EAS) AF: 0.420 AC: 2169 AN: 5170

South Asian (SAS) AF: 0.439 AC: 2114 AN: 4818

European-Finnish (FIN) AF: 0.488 AC: 5166 AN: 10584

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.582 AC: 39578 AN: 67972

Other (OTH) AF: 0.490 AC: 1035 AN: 2112

Alfa AF: 0.535 Hom.: 11593

Bravo AF: 0.516

Asia WGS AF: 0.407 AC: 1411 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.46
DANN	Benign	0.55
PhyloP100		-0.94

Splicing

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

Other links and lift over

dbSNP: rs202546; hg19: chr20-1663539;