chr18-63902437-C-G

Variant names:

• chr18-63902437-C-G
• rs758753971
• NM_002575.3:c.712C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002575.3(SERPINB2):​c.712C>G​(p.Arg238Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,612,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R238H) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SERPINB2 NM_002575.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.67
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19100487).

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.712C>G	p.Arg238Gly	missense	Exon 7 of 8	NP_002566.1	P05120
	SERPINB2	NM_001143818.2		c.712C>G	p.Arg238Gly	missense	Exon 8 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.712C>G	p.Arg238Gly	missense	Exon 7 of 8	ENSP00000299502.4	P05120
	ENSG00000289724	ENST00000418725.1	TSL:5	c.340C>G	p.Arg114Gly	missense	Exon 4 of 7	ENSP00000392381.1	H7C004
	SERPINB2	ENST00000457692.5	TSL:5	c.712C>G	p.Arg238Gly	missense	Exon 8 of 9	ENSP00000401645.1	P05120

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152074 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460794 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726720

African (AFR) AF: 0.0000299 AC: 1 AN: 33414

American (AMR) AF: 0.00 AC: 0 AN: 44614

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26074

East Asian (EAS) AF: 0.00 AC: 0 AN: 39668

South Asian (SAS) AF: 0.00 AC: 0 AN: 86166

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53388

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111392

Other (OTH) AF: 0.00 AC: 0 AN: 60324

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152074 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74278

African (AFR) AF: 0.0000724 AC: 3 AN: 41414

American (AMR) AF: 0.00 AC: 0 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.048	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	19
DANN	Benign	0.94
DEOGEN2	Benign	0.36	T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.64	T
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.59	T
MutationAssessor	Benign	1.6	L
PhyloP100		2.7
PrimateAI	Benign	0.19	T
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.22
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.018	D
Polyphen		0.23	B
Vest4		0.20
MutPred		0.53		Gain of methylation at K240 (P = 0.0542)
MVP		0.42
MPC		0.021
ClinPred		0.59	D
GERP RS		2.4
Varity_R		0.59
gMVP		0.51
Mutation Taster		=74/26	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: rs758753971; hg19: chr18-61569671;