NM_002575.3:c.536-4G>A

Variant names:

• chr18-63901736-G-A
• rs6099
• NM_002575.3:c.536-4G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002575.3(SERPINB2):​c.536-4G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00411 in 1,536,562 control chromosomes in the GnomAD database, including 251 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.022 (145 hom., cov: 32)
  • Exomes 𝑓: 0.0021 (106 hom.)
• Consequence: SERPINB2 NM_002575.3 splice_region, intron
• Scores: Splicing: ADA: 0.0001054
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.70
• Publications: 3 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 18-63901736-G-A is Benign according to our data. Variant chr18-63901736-G-A is described in ClinVar as [Benign]. Clinvar id is 780481.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINB2	NM_002575.3	c.536-4G>A		splice_region_variant, intron_variant	Intron 5 of 7	ENST00000299502.9	NP_002566.1
SERPINB2	NM_001143818.2	c.536-4G>A		splice_region_variant, intron_variant	Intron 6 of 8		NP_001137290.1
SERPINB2	XM_024451192.2	c.536-4G>A		splice_region_variant, intron_variant	Intron 5 of 7		XP_024306960.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINB2	ENST00000299502.9	c.536-4G>A		splice_region_variant, intron_variant	Intron 5 of 7	1	NM_002575.3	ENSP00000299502.4
ENSG00000289724	ENST00000418725.1	c.164-4G>A		splice_region_variant, intron_variant	Intron 2 of 6	5		ENSP00000392381.1

Frequencies

GnomAD3 genomes AF: 0.0225 AC: 3415 AN: 152084 Hom.: 145 Cov.: 32

Gnomad AFR AF: 0.0779

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00905

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: 0.000206

Gnomad OTH AF: 0.0187

GnomAD2 exomes AF: 0.00597 AC: 1131 AN: 189408 AF XY: 0.00391

Gnomad AFR exome AF: 0.0795

Gnomad AMR exome AF: 0.00397

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000146

Gnomad OTH exome AF: 0.00358

GnomAD4 exome AF: 0.00209 AC: 2891 AN: 1384360 Hom.: 106 Cov.: 29 AF XY: 0.00185 AC XY: 1269 AN XY: 685976

African (AFR) AF: 0.0845 AC: 2410 AN: 28530

American (AMR) AF: 0.00451 AC: 114 AN: 25256

Ashkenazi Jewish (ASJ) AF: 0.0000428 AC: 1 AN: 23344

East Asian (EAS) AF: 0.00 AC: 0 AN: 35874

South Asian (SAS) AF: 0.0000840 AC: 6 AN: 71458

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52602

Middle Eastern (MID) AF: 0.00181 AC: 10 AN: 5540

European-Non Finnish (NFE) AF: 0.0000572 AC: 62 AN: 1084746

Other (OTH) AF: 0.00505 AC: 288 AN: 57010

GnomAD4 genome AF: 0.0225 AC: 3418 AN: 152202 Hom.: 145 Cov.: 32 AF XY: 0.0218 AC XY: 1624 AN XY: 74412

African (AFR) AF: 0.0777 AC: 3226 AN: 41506

American (AMR) AF: 0.00904 AC: 138 AN: 15268

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 68008

Other (OTH) AF: 0.0185 AC: 39 AN: 2112

Alfa AF: 0.00820 Hom.: 57

Bravo AF: 0.0256

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.44
DANN	Benign	0.58
PhyloP100		-2.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00011
dbscSNV1_RF	Benign	0.0
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: rs6099; hg19: chr18-61568970;