NM_002575.3:c.405G>A

Variant names:

• chr18-63897207-G-A
• rs140108044
• NM_002575.3:c.405G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_002575.3(SERPINB2):​c.405G>A​(p.Ala135Ala) 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
• Publications: 2 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.011).
• 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.
• BS2: High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINB2	NM_002575.3	c.405G>A	p.Ala135Ala	synonymous_variant	Exon 4 of 8	ENST00000299502.9	NP_002566.1
SERPINB2	NM_001143818.2	c.405G>A	p.Ala135Ala	synonymous_variant	Exon 5 of 9		NP_001137290.1
SERPINB2	XM_024451192.2	c.405G>A	p.Ala135Ala	synonymous_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.405G>A	p.Ala135Ala	synonymous_variant	Exon 4 of 8	1	NM_002575.3	ENSP00000299502.4
ENSG00000289724	ENST00000418725.1	c.33G>A	p.Ala11Ala	synonymous_variant	Exon 1 of 7	5		ENSP00000392381.1

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

GnomAD2 exomes AF: 0.000802 AC: 197 AN: 245546 AF XY: 0.000873

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 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

African (AFR) AF: 0.0000906 AC: 3 AN: 33120

American (AMR) AF: 0.0000231 AC: 1 AN: 43356

Ashkenazi Jewish (ASJ) AF: 0.0000770 AC: 2 AN: 25982

East Asian (EAS) AF: 0.00 AC: 0 AN: 39524

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85218

European-Finnish (FIN) AF: 0.00238 AC: 127 AN: 53356

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5738

European-Non Finnish (NFE) AF: 0.00106 AC: 1172 AN: 1109828

Other (OTH) AF: 0.000715 AC: 43 AN: 60138

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

African (AFR) AF: 0.000120 AC: 5 AN: 41578

American (AMR) AF: 0.0000654 AC: 1 AN: 15298

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00198 AC: 21 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00173 AC: 118 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2116

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

Aug 28, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.37
DANN	Benign	0.81
PhyloP100		-3.9
PromoterAI		-0.051	Neutral
Mutation Taster		=100/0	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: rs140108044; hg19: chr18-61564441;