chr20-1677612-C-T

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000340424.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIRPB3P	ENST00000340424.4	TSL:6	n.461-6415G>A		intron	N/A
	ENSG00000296776	ENST00000741926.1		n.136-8572G>A		intron	N/A

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 v4.9

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;