chr18-63897215-G-A

Variant names:

• chr18-63897215-G-A
• rs760053054
• NM_002575.3:c.413G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002575.3(SERPINB2):​c.413G>A​(p.Arg138Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000089 in 1,606,990 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. R138L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000099 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000088 (0 hom.)
• Consequence: SERPINB2 NM_002575.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.391
• Publications: 0 publications found

Genes affected

SERPINB2 (HGNC:8584): (serpin family B member 2) Predicted to enable serine-type endopeptidase inhibitor activity. Predicted to be involved in negative regulation of endopeptidase activity. Predicted to be located in extracellular region and plasma membrane. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000289724 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04544586).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINB2	NM_002575.3	c.413G>A	p.Arg138Gln	missense_variant	Exon 4 of 8	ENST00000299502.9	NP_002566.1
SERPINB2	NM_001143818.2	c.413G>A	p.Arg138Gln	missense_variant	Exon 5 of 9		NP_001137290.1
SERPINB2	XM_024451192.2	c.413G>A	p.Arg138Gln	missense_variant	Exon 4 of 8		XP_024306960.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINB2	ENST00000299502.9	c.413G>A	p.Arg138Gln	missense_variant	Exon 4 of 8	1	NM_002575.3	ENSP00000299502.4
ENSG00000289724	ENST00000418725.1	c.41G>A	p.Arg14Gln	missense_variant	Exon 1 of 7	5		ENSP00000392381.1

Frequencies

GnomAD3 genomes AF: 0.0000986 AC: 15 AN: 152156 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000102 AC: 25 AN: 245062 AF XY: 0.0000755

Gnomad AFR exome AF: 0.000125

Gnomad AMR exome AF: 0.000216

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000107

Gnomad OTH exome AF: 0.000167

GnomAD4 exome AF: 0.0000880 AC: 128 AN: 1454834 Hom.: 0 Cov.: 31 AF XY: 0.0000788 AC XY: 57 AN XY: 723646

African (AFR) AF: 0.0000908 AC: 3 AN: 33042

American (AMR) AF: 0.000186 AC: 8 AN: 43074

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25918

East Asian (EAS) AF: 0.00 AC: 0 AN: 39476

South Asian (SAS) AF: 0.0000471 AC: 4 AN: 84922

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53314

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5734

European-Non Finnish (NFE) AF: 0.0000929 AC: 103 AN: 1109286

Other (OTH) AF: 0.000133 AC: 8 AN: 60068

GnomAD4 genome AF: 0.0000986 AC: 15 AN: 152156 Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3 AN XY: 74332

African (AFR) AF: 0.0000724 AC: 3 AN: 41432

American (AMR) AF: 0.000131 AC: 2 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000988 Hom.: 0

Bravo AF: 0.0000567

ExAC AF: 0.0000741 AC: 9

EpiCase AF: 0.000219

EpiControl AF: 0.000179

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T;T;T
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.79	.;T;T
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.045	T;T;T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	0.39	N;N;.
PhyloP100		-0.39
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.24	N;N;N
REVEL	Benign	0.16
Sift	Benign	0.26	T;T;T
Sift4G	Benign	0.27	T;T;T
Polyphen		0.27	B;B;.
Vest4		0.11
MVP		0.30
MPC		0.017
ClinPred		0.013	T
GERP RS		-2.3
PromoterAI		-0.0084	Neutral
Varity_R		0.11
gMVP		0.23
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs760053054; hg19: chr18-61564449;