20-1475434-G-A

Position:

• chr20-1475434-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001122962.2(SIRPB2):​c.*733C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 152,280 control chromosomes in the GnomAD database, including 943 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 0.10 (943 hom., cov: 32)
  • Exomes 𝑓: 0.11 (0 hom.)
• Consequence: SIRPB2 NM_001122962.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0870

Genes affected

SIRPB2 (HGNC:16247): (signal regulatory protein beta 2) Predicted to be integral component of membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIRPB2	NM_001122962.2	c.*733C>T		3_prime_UTR_variant	5/5	ENST00000359801.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIRPB2	ENST00000359801.8	c.*733C>T		3_prime_UTR_variant	5/5	2	NM_001122962.2	P1
SIRPB2	ENST00000481731.5	c.860-1564C>T		intron_variant, NMD_transcript_variant		5
SIRPB2	ENST00000486775.5	c.860-1564C>T		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15602 AN: 152124 Hom.: 943 Cov.: 32

Gnomad AFR AF: 0.0661

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.0890

Gnomad EAS AF: 0.00539

Gnomad SAS AF: 0.0751

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.104

GnomAD4 exome AF: 0.105 AC: 4 AN: 38 Hom.: 0 Cov.: 0 AF XY: 0.0385 AC XY: 1 AN XY: 26

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.125

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.103 AC: 15609 AN: 152242 Hom.: 943 Cov.: 32 AF XY: 0.102 AC XY: 7622 AN XY: 74438

Gnomad4 AFR AF: 0.0660

Gnomad4 AMR AF: 0.180

Gnomad4 ASJ AF: 0.0890

Gnomad4 EAS AF: 0.00560

Gnomad4 SAS AF: 0.0747

Gnomad4 FIN AF: 0.107

Gnomad4 NFE AF: 0.117

Gnomad4 OTH AF: 0.105

Alfa AF: 0.116 Hom.: 1582

Bravo AF: 0.109

Asia WGS AF: 0.0510 AC: 178 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.4
DANN	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs1884393; hg19: chr20-1456079;