20-1478415-T-G

Variant names:

• chr20-1478415-T-G
• rs6042507
• NM_001122962.2:c.644A>C

Variant summary

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

The NM_001122962.2(SIRPB2):​c.644A>C​(p.Glu215Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.899 in 1,614,080 control chromosomes in the GnomAD database, including 653,398 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.92 (63898 hom., cov: 32)
  • Exomes 𝑓: 0.90 (589500 hom.)
• Consequence: SIRPB2 NM_001122962.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.291

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 (MetaRNN=6.808541E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.973 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIRPB2	NM_001122962.2	c.644A>C	p.Glu215Ala	missense_variant	Exon 3 of 5	ENST00000359801.8	NP_001116434.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIRPB2	ENST00000359801.8	c.644A>C	p.Glu215Ala	missense_variant	Exon 3 of 5	2	NM_001122962.2	ENSP00000352849.3

Frequencies

GnomAD3 genomes AF: 0.915 AC: 139172 AN: 152100 Hom.: 63836 Cov.: 32

Gnomad AFR AF: 0.976

Gnomad AMI AF: 0.975

Gnomad AMR AF: 0.911

Gnomad ASJ AF: 0.847

Gnomad EAS AF: 0.996

Gnomad SAS AF: 0.973

Gnomad FIN AF: 0.835

Gnomad MID AF: 0.864

Gnomad NFE AF: 0.884

Gnomad OTH AF: 0.898

GnomAD3 exomes AF: 0.913 AC: 227320 AN: 249052 Hom.: 104016 AF XY: 0.911 AC XY: 123300 AN XY: 135334

Gnomad AFR exome AF: 0.980

Gnomad AMR exome AF: 0.930

Gnomad ASJ exome AF: 0.848

Gnomad EAS exome AF: 0.996

Gnomad SAS exome AF: 0.968

Gnomad FIN exome AF: 0.853

Gnomad NFE exome AF: 0.888

Gnomad OTH exome AF: 0.892

GnomAD4 exome AF: 0.897 AC: 1311829 AN: 1461862 Hom.: 589500 Cov.: 76 AF XY: 0.898 AC XY: 653409 AN XY: 727234

Gnomad4 AFR exome AF: 0.979

Gnomad4 AMR exome AF: 0.927

Gnomad4 ASJ exome AF: 0.849

Gnomad4 EAS exome AF: 0.999

Gnomad4 SAS exome AF: 0.967

Gnomad4 FIN exome AF: 0.859

Gnomad4 NFE exome AF: 0.888

Gnomad4 OTH exome AF: 0.899

GnomAD4 genome AF: 0.915 AC: 139293 AN: 152218 Hom.: 63898 Cov.: 32 AF XY: 0.914 AC XY: 67998 AN XY: 74390

Gnomad4 AFR AF: 0.976

Gnomad4 AMR AF: 0.911

Gnomad4 ASJ AF: 0.847

Gnomad4 EAS AF: 0.996

Gnomad4 SAS AF: 0.972

Gnomad4 FIN AF: 0.835

Gnomad4 NFE AF: 0.884

Gnomad4 OTH AF: 0.899

Alfa AF: 0.887 Hom.: 137067

Bravo AF: 0.921

TwinsUK AF: 0.888 AC: 3294

ALSPAC AF: 0.896 AC: 3452

ESP6500AA AF: 0.978 AC: 3066

ESP6500EA AF: 0.885 AC: 6342

ExAC AF: 0.915 AC: 110121

EpiCase AF: 0.880

EpiControl AF: 0.883

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.047
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	8.0
DANN	Benign	0.87
DEOGEN2	Benign	0.0065	T;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.15	T;T
MetaRNN	Benign	6.8e-7	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.45	N;.
PrimateAI	Benign	0.24	T
PROVEAN	Benign	1.4	N;N
REVEL	Benign	0.066
Sift	Benign	0.21	T;T
Sift4G	Benign	0.32	T;T
Polyphen		0.0	B;.
Vest4		0.013
MPC		0.049
ClinPred		0.011	T
GERP RS		3.0
Varity_R		0.11
gMVP		0.10

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: rs6042507; hg19: chr20-1459060;