Variant 18-63901736-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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

Variant links:

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]

SERPINB2 links:

ENSG00000289724 (HGNC:):

ENSG00000289724 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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	Effect	MANE	Protein	UniProt
SERPINB2	NM_002575.3 linkuse as main transcript	c.536-4G>A	splice_region_variant, intron_variant	ENST00000299502.9	NP_002566.1	P05120
SERPINB2	NM_001143818.2 linkuse as main transcript	c.536-4G>A	splice_region_variant, intron_variant		NP_001137290.1	P05120
SERPINB2	XM_024451192.2 linkuse as main transcript	c.536-4G>A	splice_region_variant, intron_variant		XP_024306960.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERPINB2	ENST00000299502.9 linkuse as main transcript	c.536-4G>A		splice_region_variant, intron_variant		1	NM_002575.3	ENSP00000299502.4		P05120
ENSG00000289724	ENST00000397996.6 linkuse as main transcript	c.164-4G>A		splice_region_variant, intron_variant		5		ENSP00000381082.2		H7BYS2

Frequencies

GnomAD3 genomes

AF:

0.0225

AC:

3415

AN:

152084

Hom.:

145

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.00597

AC:

1131

AN:

189408

Hom.:

AF XY:

0.00391

AC XY:

409

AN XY:

104594

show subpopulations

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 SAS exome

AF:

0.0000480

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.:

AF XY:

0.00185

AC XY:

1269

AN XY:

685976

show subpopulations

Gnomad4 AFR exome

AF:

0.0845

Gnomad4 AMR exome

AF:

0.00451

Gnomad4 ASJ exome

AF:

0.0000428

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000840

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000572

Gnomad4 OTH exome

AF:

0.00505

GnomAD4 genome

AF:

0.0225

AC:

3418

AN:

152202

Hom.:

145

Cov.:

AF XY:

0.0218

AC XY:

1624

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.0777

Gnomad4 AMR

AF:

0.00904

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.0185

Alfa

AF:

0.00604

Hom.:

Bravo

AF:

0.0256

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

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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

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over