18-63897207-G-A

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_002575.3(SERPINB2):c.405G>A(p.Ala135=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000929 in 1,608,566 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00095 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00093 (5 hom.)
• Consequence: SERPINB2 NM_002575.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.93

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]

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 18-63897207-G-A is Benign according to our data. Variant chr18-63897207-G-A is described in ClinVar as [Benign]. Clinvar id is 744522.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.93 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERPINB2	NM_002575.3	c.405G>A	p.Ala135=	synonymous_variant	4/8	ENST00000299502.9
SERPINB2	NM_001143818.2	c.405G>A	p.Ala135=	synonymous_variant	5/9
SERPINB2	XM_024451192.2	c.405G>A	p.Ala135=	synonymous_variant	4/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINB2	ENST00000299502.9	c.405G>A	p.Ala135=	synonymous_variant	4/8	1	NM_002575.3	P1

Frequencies

GnomAD3 genomes AF: 0.000953 AC: 145 AN: 152188 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00198

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00173

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000802 AC: 197 AN: 245546 Hom.: 0 AF XY: 0.000873 AC XY: 116 AN XY: 132808

Gnomad AFR exome AF: 0.0000622

Gnomad AMR exome AF: 0.0000307

Gnomad ASJ exome AF: 0.000101

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00213

Gnomad NFE exome AF: 0.00129

Gnomad OTH exome AF: 0.000501

GnomAD4 exome AF: 0.000926 AC: 1349 AN: 1456260 Hom.: 5 Cov.: 31 AF XY: 0.000977 AC XY: 708 AN XY: 724424

Gnomad4 AFR exome AF: 0.0000906

Gnomad4 AMR exome AF: 0.0000231

Gnomad4 ASJ exome AF: 0.0000770

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000117

Gnomad4 FIN exome AF: 0.00238

Gnomad4 NFE exome AF: 0.00106

Gnomad4 OTH exome AF: 0.000715

GnomAD4 genome AF: 0.000952 AC: 145 AN: 152306 Hom.: 0 Cov.: 33 AF XY: 0.000873 AC XY: 65 AN XY: 74476

Gnomad4 AFR AF: 0.000120

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00198

Gnomad4 NFE AF: 0.00173

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00113 Hom.: 0

Bravo AF: 0.000604

EpiCase AF: 0.00169

EpiControl AF: 0.000835

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

Invitae

Aug 28, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
Cadd	Benign	0.37
Dann	Benign	0.81

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: rs140108044; hg19: chr18-61564441;