ENST00000340424.4:n.461-6415G>A

Variant names:

• chr20-1677612-C-T
• rs6034368
• ENST00000340424.4:n.461-6415G>A

Variant summary

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

The ENST00000340424.4(SIRPB3P):​n.461-6415G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 152,060 control chromosomes in the GnomAD database, including 5,276 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 (5276 hom., cov: 32)
• Consequence: SIRPB3P ENST00000340424.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.379
• 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIRPG	XM_011529286.3	c.-27+8720G>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.461-6415G>A		intron_variant	Intron 2 of 4	6
ENSG00000296776	ENST00000741926.1	n.136-8572G>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37196 AN: 151942 Hom.: 5274 Cov.: 32

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.587

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.281

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.279

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

GnomAD4 genome AF: 0.245 AC: 37209 AN: 152060 Hom.: 5276 Cov.: 32 AF XY: 0.252 AC XY: 18753 AN XY: 74340

African (AFR) AF: 0.152 AC: 6287 AN: 41464

American (AMR) AF: 0.253 AC: 3863 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.321 AC: 1112 AN: 3468

East Asian (EAS) AF: 0.586 AC: 3026 AN: 5160

South Asian (SAS) AF: 0.460 AC: 2220 AN: 4824

European-Finnish (FIN) AF: 0.281 AC: 2971 AN: 10576

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

European-Non Finnish (NFE) AF: 0.249 AC: 16892 AN: 67972

Other (OTH) AF: 0.283 AC: 598 AN: 2112

Alfa AF: 0.257 Hom.: 2949

Bravo AF: 0.235

Asia WGS AF: 0.514 AC: 1788 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	6.0
DANN	Benign	0.36
PhyloP100		-0.38

Splicing

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

Other links and lift over

dbSNP: rs6034368; hg19: chr20-1658258;