Genetic Variant NM_030666.4:c.568-9A>T (chr6-2836032-T-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_030666.4(SERPINB1):c.568-9A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.566 in 1,613,456 control chromosomes in the GnomAD database, including 260,307 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.54 ( 22649 hom., cov: 32)

Exomes 𝑓: 0.57 ( 237658 hom. )

Consequence

SERPINB1
NM_030666.4 intron

Scores

Splicing: ADA: 0.00003464

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.102

Publications

9 publications found

Variant links:

Genes affected

SERPINB1 (HGNC:3311): (serpin family B member 1) The protein encoded by this gene is a member of the serpin family of proteinase inhibitors. Members of this family maintain homeostasis by neutralizing overexpressed proteinase activity through their function as suicide substrates. This protein inhibits the neutrophil-derived proteinases neutrophil elastase, cathepsin G, and proteinase-3 and thus protects tissues from damage at inflammatory sites. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]

SERPINB1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 6-2836032-T-A is Benign according to our data. Variant chr6-2836032-T-A is described in ClinVar as Benign. ClinVar VariationId is 1244118.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.62 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030666.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SERPINB1	NM_030666.4	MANE Select	c.568-9A>T	intron	N/A	NP_109591.1	P30740-1
SERPINB1	NR_073111.2		n.760-9A>T	intron	N/A
SERPINB1	NR_073112.2		n.628-13A>T	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SERPINB1	ENST00000380739.6	TSL:1 MANE Select	c.568-9A>T	intron	N/A	ENSP00000370115.5	P30740-1
SERPINB1	ENST00000878907.1		c.568-9A>T	intron	N/A	ENSP00000548966.1
SERPINB1	ENST00000878908.1		c.568-9A>T	intron	N/A	ENSP00000548967.1

Frequencies

GnomAD3 genomes

AF:

0.542

AC:

82372

AN:

151902

Hom.:

22621

Cov.:

show subpopulations

Gnomad AFR

AF:

0.473

Gnomad AMI

AF:

0.678

Gnomad AMR

AF:

0.630

Gnomad ASJ

AF:

0.577

Gnomad EAS

AF:

0.567

Gnomad SAS

AF:

0.568

Gnomad FIN

AF:

0.434

Gnomad MID

AF:

0.646

Gnomad NFE

AF:

0.573

Gnomad OTH

AF:

0.570

GnomAD2 exomes

AF:

0.575

AC:

144312

AN:

251048

AF XY:

0.573

show subpopulations

Gnomad AFR exome

AF:

0.463

Gnomad AMR exome

AF:

0.716

Gnomad ASJ exome

AF:

0.589

Gnomad EAS exome

AF:

0.561

Gnomad FIN exome

AF:

0.441

Gnomad NFE exome

AF:

0.576

Gnomad OTH exome

AF:

0.578

GnomAD4 exome

AF:

0.568

AC:

830314

AN:

1461436

Hom.:

237658

Cov.:

AF XY:

0.569

AC XY:

413505

AN XY:

727046

show subpopulations

African (AFR)

AF:

0.466

AC:

15565

AN:

33424

American (AMR)

AF:

0.702

AC:

31329

AN:

44652

Ashkenazi Jewish (ASJ)

AF:

0.588

AC:

15358

AN:

26124

East Asian (EAS)

AF:

0.569

AC:

22591

AN:

39696

South Asian (SAS)

AF:

0.573

AC:

49397

AN:

86234

European-Finnish (FIN)

AF:

0.449

AC:

23973

AN:

53398

Middle Eastern (MID)

AF:

0.621

AC:

3581

AN:

5768

European-Non Finnish (NFE)

AF:

0.571

AC:

634822

AN:

1111772

Other (OTH)

AF:

0.558

AC:

33698

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

18945

37891

56836

75782

94727

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17604

35208

52812

70416

88020

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.542

AC:

82448

AN:

152020

Hom.:

22649

Cov.:

AF XY:

0.540

AC XY:

40116

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.474

AC:

19611

AN:

41416

American (AMR)

AF:

0.630

AC:

9625

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.577

AC:

1999

AN:

3464

East Asian (EAS)

AF:

0.567

AC:

2935

AN:

5176

South Asian (SAS)

AF:

0.569

AC:

2742

AN:

4822

European-Finnish (FIN)

AF:

0.434

AC:

4596

AN:

10596

Middle Eastern (MID)

AF:

0.653

AC:

192

AN:

294

European-Non Finnish (NFE)

AF:

0.573

AC:

38928

AN:

67956

Other (OTH)

AF:

0.570

AC:

1202

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1939

3878

5817

7756

9695

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

722

1444

2166

2888

3610

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.537

Hom.:

6233

Bravo

AF:

0.556

Asia WGS

AF:

0.571

AC:

1982

AN:

3472

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

9.5

(source)

DANN

Benign

0.73

PhyloP100

0.10

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000035

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.10

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over