20-1629905-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_018556.4(SIRPG):c.*3-269A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.711 in 151,976 control chromosomes in the GnomAD database, including 38,698 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.71 (38698 hom., cov: 30)
• Consequence: SIRPG NM_018556.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.509

Genes affected

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BP6: Variant 20-1629905-T-C is Benign according to our data. Variant chr20-1629905-T-C is described in ClinVar as [Benign]. Clinvar id is 1276615.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.83 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIRPG	NM_018556.4	c.*3-269A>G		intron_variant		ENST00000303415.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIRPG	ENST00000303415.7	c.*3-269A>G		intron_variant		1	NM_018556.4	P2

Frequencies

GnomAD3 genomes AF: 0.711 AC: 107944 AN: 151858 Hom.: 38671 Cov.: 30

Gnomad AFR AF: 0.765

Gnomad AMI AF: 0.545

Gnomad AMR AF: 0.750

Gnomad ASJ AF: 0.737

Gnomad EAS AF: 0.836

Gnomad SAS AF: 0.853

Gnomad FIN AF: 0.698

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.652

Gnomad OTH AF: 0.717

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

GnomAD4 genome AF: 0.711 AC: 108028 AN: 151976 Hom.: 38698 Cov.: 30 AF XY: 0.718 AC XY: 53317 AN XY: 74286

Gnomad4 AFR AF: 0.765

Gnomad4 AMR AF: 0.750

Gnomad4 ASJ AF: 0.737

Gnomad4 EAS AF: 0.837

Gnomad4 SAS AF: 0.852

Gnomad4 FIN AF: 0.698

Gnomad4 NFE AF: 0.652

Gnomad4 OTH AF: 0.719

Alfa AF: 0.670 Hom.: 44159

Bravo AF: 0.712

Asia WGS AF: 0.822 AC: 2856 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 17, 2019

This variant is associated with the following publications: (PMID: 30337675) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	2.6
Dann	Benign	0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2281808; hg19: chr20-1610551;