18-63897160-A-G

Variant names:

• chr18-63897160-A-G
• rs6098
• NM_002575.3:c.358A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002575.3(SERPINB2):​c.358A>G​(p.Asn120Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 1,611,998 control chromosomes in the GnomAD database, including 51,138 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.29 (6841 hom., cov: 32)
  • Exomes 𝑓: 0.24 (44297 hom.)
• Consequence: SERPINB2 NM_002575.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.809
• Publications: 38 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.001850158).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.463 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002575.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINB2	NM_002575.3	MANE Select	c.358A>G	p.Asn120Asp	missense	Exon 4 of 8	NP_002566.1	P05120
	SERPINB2	NM_001143818.2		c.358A>G	p.Asn120Asp	missense	Exon 5 of 9	NP_001137290.1	P05120

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINB2	ENST00000299502.9	TSL:1 MANE Select	c.358A>G	p.Asn120Asp	missense	Exon 4 of 8	ENSP00000299502.4	P05120
	SERPINB2	ENST00000457692.5	TSL:5	c.358A>G	p.Asn120Asp	missense	Exon 5 of 9	ENSP00000401645.1	P05120
	SERPINB2	ENST00000942451.1		c.358A>G	p.Asn120Asp	missense	Exon 5 of 9	ENSP00000612510.1

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43494 AN: 151964 Hom.: 6820 Cov.: 32

Gnomad AFR AF: 0.363

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.370

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.479

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.304

GnomAD2 exomes AF: 0.284 AC: 71089 AN: 250042 AF XY: 0.276

Gnomad AFR exome AF: 0.368

Gnomad AMR exome AF: 0.425

Gnomad ASJ exome AF: 0.189

Gnomad EAS exome AF: 0.471

Gnomad FIN exome AF: 0.233

Gnomad NFE exome AF: 0.220

Gnomad OTH exome AF: 0.267

GnomAD4 exome AF: 0.239 AC: 349163 AN: 1459916 Hom.: 44297 Cov.: 32 AF XY: 0.240 AC XY: 173944 AN XY: 726276

African (AFR) AF: 0.370 AC: 12342 AN: 33386

American (AMR) AF: 0.414 AC: 18385 AN: 44432

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 4860 AN: 26072

East Asian (EAS) AF: 0.404 AC: 15990 AN: 39592

South Asian (SAS) AF: 0.279 AC: 23994 AN: 85970

European-Finnish (FIN) AF: 0.228 AC: 12157 AN: 53358

Middle Eastern (MID) AF: 0.302 AC: 1737 AN: 5752

European-Non Finnish (NFE) AF: 0.220 AC: 244024 AN: 1111052

Other (OTH) AF: 0.260 AC: 15674 AN: 60302

GnomAD4 genome AF: 0.286 AC: 43550 AN: 152082 Hom.: 6841 Cov.: 32 AF XY: 0.290 AC XY: 21525 AN XY: 74326

African (AFR) AF: 0.363 AC: 15066 AN: 41490

American (AMR) AF: 0.370 AC: 5659 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 638 AN: 3468

East Asian (EAS) AF: 0.479 AC: 2475 AN: 5166

South Asian (SAS) AF: 0.297 AC: 1432 AN: 4814

European-Finnish (FIN) AF: 0.233 AC: 2466 AN: 10566

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.220 AC: 14943 AN: 67980

Other (OTH) AF: 0.310 AC: 653 AN: 2106

Alfa AF: 0.243 Hom.: 19614

Bravo AF: 0.302

TwinsUK AF: 0.202 AC: 748

ALSPAC AF: 0.208 AC: 803

ESP6500AA AF: 0.369 AC: 1626

ESP6500EA AF: 0.218 AC: 1878

ExAC AF: 0.279 AC: 33823

Asia WGS AF: 0.389 AC: 1350 AN: 3478

EpiCase AF: 0.229

EpiControl AF: 0.224

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.055
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	14
DANN	Benign	0.83
DEOGEN2	Benign	0.10	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.028	T
MetaRNN	Benign	0.0019	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-1.4	N
PhyloP100		0.81
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.060	N
REVEL	Benign	0.14
Sift	Benign	0.80	T
Sift4G	Benign	0.67	T
Polyphen		0.0	B
Vest4		0.017
MPC		0.016
ClinPred		0.0026	T
GERP RS		4.1
PromoterAI		-0.0066	Neutral
Varity_R		0.17
gMVP		0.084
Mutation Taster		=100/0	polymorphism (auto)

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: rs6098; hg19: chr18-61564394; COSMIC: COSV55092626; COSMIC: COSV55092626;