dbSNP rs17091162: SERPINA3:c.1068+404C>A (chr14-94622895-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001085.5(SERPINA3):c.1068+404C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 309,622 control chromosomes in the GnomAD database, including 8,775 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.25 ( 4775 hom., cov: 33)

Exomes 𝑓: 0.22 ( 4000 hom. )

Consequence

SERPINA3
NM_001085.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.272

Publications

5 publications found

Variant links:

Genes affected

SERPINA3 (HGNC:16): (serpin family A member 3) The protein encoded by this gene is a member of the serpin family of proteins, a group of proteins that inhibit serine proteases. This gene is one in a cluster of serpin genes located on the q arm of chromosome 14. Polymorphisms in this protein appear to be tissue specific and influence protease targeting. Variations in this protein's sequence have been implicated in Alzheimer's disease, and deficiency of this protein has been associated with liver disease. Mutations have been identified in patients with Parkinson disease and chronic obstructive pulmonary disease. [provided by RefSeq, Jun 2020]

SERPINA3 links:

ENSG00000273259 (HGNC:):

ENSG00000273259 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SERPINA3	NM_001085.5 link	c.1068+404C>A	intron_variant	Intron 4 of 4	ENST00000393078.5	NP_001076.2	P01011-1A0A024R6P0
SERPINA3	NM_001384672.1 link	c.1068+404C>A	intron_variant	Intron 4 of 4		NP_001371601.1
SERPINA3	NM_001384673.1 link	c.1068+404C>A	intron_variant	Intron 5 of 5		NP_001371602.1
SERPINA3	NM_001384674.1 link	c.1068+404C>A	intron_variant	Intron 5 of 5		NP_001371603.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINA3	ENST00000393078.5 link	c.1068+404C>A		intron_variant	Intron 4 of 4	1	NM_001085.5	ENSP00000376793.3		P01011-1
ENSG00000273259	ENST00000553947.1 link	n.*1894+404C>A		intron_variant	Intron 7 of 7	2		ENSP00000452367.2		G3V5I3

Frequencies

GnomAD3 genomes

AF:

0.249

AC:

37836

AN:

151968

Hom.:

4771

Cov.:

show subpopulations

Gnomad AFR

AF:

0.293

Gnomad AMI

AF:

0.234

Gnomad AMR

AF:

0.247

Gnomad ASJ

AF:

0.343

Gnomad EAS

AF:

0.165

Gnomad SAS

AF:

0.226

Gnomad FIN

AF:

0.226

Gnomad MID

AF:

0.364

Gnomad NFE

AF:

0.229

Gnomad OTH

AF:

0.260

GnomAD4 exome

AF:

0.219

AC:

34500

AN:

157536

Hom.:

4000

AF XY:

0.218

AC XY:

18214

AN XY:

83418

show subpopulations

African (AFR)

AF:

0.300

AC:

1525

AN:

5084

American (AMR)

AF:

0.234

AC:

1876

AN:

8000

Ashkenazi Jewish (ASJ)

AF:

0.316

AC:

1243

AN:

3936

East Asian (EAS)

AF:

0.144

AC:

1104

AN:

7660

South Asian (SAS)

AF:

0.210

AC:

5531

AN:

26278

European-Finnish (FIN)

AF:

0.198

AC:

1379

AN:

6966

Middle Eastern (MID)

AF:

0.278

AC:

161

AN:

580

European-Non Finnish (NFE)

AF:

0.218

AC:

19848

AN:

91064

Other (OTH)

AF:

0.230

AC:

1833

AN:

7968

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

1255

2509

3764

5018

6273

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

192

384

576

768

960

<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:

0.249

AC:

37849

AN:

152086

Hom.:

4775

Cov.:

AF XY:

0.248

AC XY:

18470

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.293

AC:

12160

AN:

41458

American (AMR)

AF:

0.246

AC:

3763

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.343

AC:

1188

AN:

3468

East Asian (EAS)

AF:

0.164

AC:

850

AN:

5174

South Asian (SAS)

AF:

0.226

AC:

1090

AN:

4822

European-Finnish (FIN)

AF:

0.226

AC:

2395

AN:

10578

Middle Eastern (MID)

AF:

0.367

AC:

108

AN:

294

European-Non Finnish (NFE)

AF:

0.229

AC:

15537

AN:

67972

Other (OTH)

AF:

0.258

AC:

545

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1492

2984

4476

5968

7460

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

394

788

1182

1576

1970

<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:

0.239

Hom.:

9569

Bravo

AF:

0.254

Asia WGS

AF:

0.207

AC:

722

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

4.0

(source)

DANN

Benign

0.41

PhyloP100

0.27

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over