dbSNP rs17751769: SERPINA1:c.-5+100C>T (chr14-94390320-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000355814.8(SERPINA1):c.-5+100C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 151,834 control chromosomes in the GnomAD database, including 15,998 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 0.45 ( 15998 hom., cov: 33)

Exomes 𝑓: 0.39 ( 20 hom. )

Failed GnomAD Quality Control

Consequence

SERPINA1
ENST00000355814.8 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.797

Publications

14 publications found

Variant links:

Genes affected

SERPINA1 (HGNC:8941): (serpin family A member 1) The protein encoded by this gene is a serine protease inhibitor belonging to the serpin superfamily whose targets include elastase, plasmin, thrombin, trypsin, chymotrypsin, and plasminogen activator. This protein is produced in the liver, the bone marrow, by lymphocytic and monocytic cells in lymphoid tissue, and by the Paneth cells of the gut. Defects in this gene are associated with chronic obstructive pulmonary disease, emphysema, and chronic liver disease. Several transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Aug 2020]

SERPINA1 Gene-Disease associations (from GenCC):

alpha 1-antitrypsin deficiency
Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Genomics England PanelApp, Orphanet, Labcorp Genetics (formerly Invitae)
hemorrhagic disease due to alpha-1-antitrypsin Pittsburgh mutation
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
cystic fibrosis
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

SERPINA1 links:

ENSG00000256357 (HGNC:):

ENSG00000256357 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=-0.85).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein
SERPINA1	NM_001002235.3 link	c.-5+137C>T	intron_variant	Intron 1 of 4	NP_001002235.1
SERPINA1	NM_001002236.3 link	c.-319+137C>T	intron_variant	Intron 1 of 6	NP_001002236.1
SERPINA1	NM_001127700.2 link	c.-5+100C>T	intron_variant	Intron 1 of 4	NP_001121172.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein
SERPINA1	ENST00000355814.8 link	c.-5+100C>T	intron_variant	Intron 1 of 4	1	ENSP00000348068.4
SERPINA1	ENST00000393088.8 link	c.-319+137C>T	intron_variant	Intron 1 of 6	1	ENSP00000376803.4
SERPINA1	ENST00000404814.8 link	c.-106+137C>T	intron_variant	Intron 1 of 5	1	ENSP00000385960.4

Frequencies

GnomAD3 genomes

AF:

0.452

AC:

68531

AN:

151716

Hom.:

15990

Cov.:

show subpopulations

Gnomad AFR

AF:

0.561

Gnomad AMI

AF:

0.413

Gnomad AMR

AF:

0.303

Gnomad ASJ

AF:

0.433

Gnomad EAS

AF:

0.592

Gnomad SAS

AF:

0.477

Gnomad FIN

AF:

0.427

Gnomad MID

AF:

0.358

Gnomad NFE

AF:

0.412

Gnomad OTH

AF:

0.441

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.390

AC:

114

AN:

292

Hom.:

AF XY:

0.402

AC XY:

AN XY:

214

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AF:

0.250

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

0.667

AC:

AN:

South Asian (SAS)

AF:

0.833

AC:

AN:

European-Finnish (FIN)

AF:

0.100

AC:

AN:

Middle Eastern (MID)

AF:

0.250

AC:

AN:

European-Non Finnish (NFE)

AF:

0.372

AC:

AN:

234

Other (OTH)

AF:

0.545

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.522

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.452

AC:

68580

AN:

151834

Hom.:

15998

Cov.:

AF XY:

0.450

AC XY:

33362

AN XY:

74192

show subpopulations

African (AFR)

AF:

0.560

AC:

23192

AN:

41394

American (AMR)

AF:

0.303

AC:

4624

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.433

AC:

1501

AN:

3468

East Asian (EAS)

AF:

0.592

AC:

3044

AN:

5146

South Asian (SAS)

AF:

0.477

AC:

2298

AN:

4814

European-Finnish (FIN)

AF:

0.427

AC:

4504

AN:

10540

Middle Eastern (MID)

AF:

0.367

AC:

108

AN:

294

European-Non Finnish (NFE)

AF:

0.412

AC:

27999

AN:

67892

Other (OTH)

AF:

0.444

AC:

934

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1911

3822

5732

7643

9554

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

640

1280

1920

2560

3200

<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:

0.420

Hom.:

21120

Bravo

AF:

0.446

Asia WGS

AF:

0.489

AC:

1701

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

3.8

(source)

DANN

Benign

0.66

PhyloP100

-0.80

PromoterAI

-0.070

Neutral

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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