Genetic Variant SERPINA4:c.924-124T>A (chr14-94568005-T-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_006215.4(SERPINA4):c.924-124T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 920,980 control chromosomes in the GnomAD database, including 68,632 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 0.41 ( 13319 hom., cov: 32)

Exomes 𝑓: 0.37 ( 55313 hom. )

Consequence

SERPINA4
NM_006215.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.184

Publications

6 publications found

Variant links:

Genes affected

SERPINA4 (HGNC:8948): (serpin family A member 4) Predicted to enable serine-type endopeptidase inhibitor activity. Predicted to be involved in negative regulation of endopeptidase activity. Located in extracellular exosome. Biomarker of diabetic retinopathy. [provided by Alliance of Genome Resources, Apr 2022]

SERPINA4 links:

SERPINA5 (HGNC:8723): (serpin family A member 5) 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. This family member is a glycoprotein that can inhibit several serine proteases, including protein C and various plasminogen activators and kallikreins, and it thus plays diverse roles in hemostasis and thrombosis in multiple organs. [provided by RefSeq, Aug 2012]

SERPINA5 links:

ENSG00000294537 (HGNC:):

ENSG00000294537 links:

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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=-0.87).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SERPINA4	NM_006215.4 link	c.924-124T>A	intron_variant	Intron 3 of 4	ENST00000557004.6	NP_006206.2	P29622A0A024R6I9
SERPINA4	NM_001289032.2 link	c.1035-124T>A	intron_variant	Intron 3 of 4		NP_001275961.1	P29622
SERPINA4	NM_001289033.2 link	c.924-124T>A	intron_variant	Intron 3 of 4		NP_001275962.1	P29622A0A024R6I9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINA4	ENST00000557004.6 link	c.924-124T>A		intron_variant	Intron 3 of 4	1	NM_006215.4	ENSP00000450838.1		P29622

Frequencies

GnomAD3 genomes

AF:

0.412

AC:

62559

AN:

151900

Hom.:

13289

Cov.:

show subpopulations

Gnomad AFR

AF:

0.521

Gnomad AMI

AF:

0.211

Gnomad AMR

AF:

0.356

Gnomad ASJ

AF:

0.387

Gnomad EAS

AF:

0.404

Gnomad SAS

AF:

0.526

Gnomad FIN

AF:

0.414

Gnomad MID

AF:

0.358

Gnomad NFE

AF:

0.354

Gnomad OTH

AF:

0.419

GnomAD4 exome

AF:

0.373

AC:

286951

AN:

768958

Hom.:

55313

AF XY:

0.378

AC XY:

150223

AN XY:

397388

show subpopulations

African (AFR)

AF:

0.523

AC:

9957

AN:

19046

American (AMR)

AF:

0.339

AC:

10371

AN:

30584

Ashkenazi Jewish (ASJ)

AF:

0.391

AC:

6537

AN:

16732

East Asian (EAS)

AF:

0.427

AC:

15365

AN:

35958

South Asian (SAS)

AF:

0.515

AC:

29284

AN:

56860

European-Finnish (FIN)

AF:

0.406

AC:

16357

AN:

40290

Middle Eastern (MID)

AF:

0.404

AC:

1702

AN:

4214

European-Non Finnish (NFE)

AF:

0.346

AC:

183046

AN:

528504

Other (OTH)

AF:

0.390

AC:

14332

AN:

36770

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

8603

17206

25809

34412

43015

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4140

8280

12420

16560

20700

<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:

0.412

AC:

62648

AN:

152022

Hom.:

13319

Cov.:

AF XY:

0.415

AC XY:

30815

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.522

AC:

21637

AN:

41466

American (AMR)

AF:

0.356

AC:

5439

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.387

AC:

1342

AN:

3472

East Asian (EAS)

AF:

0.404

AC:

2073

AN:

5130

South Asian (SAS)

AF:

0.525

AC:

2529

AN:

4816

European-Finnish (FIN)

AF:

0.414

AC:

4378

AN:

10568

Middle Eastern (MID)

AF:

0.344

AC:

101

AN:

294

European-Non Finnish (NFE)

AF:

0.354

AC:

24058

AN:

67968

Other (OTH)

AF:

0.426

AC:

899

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1880

3761

5641

7522

9402

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

600

1200

1800

2400

3000

<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:

0.387

Hom.:

1428

Bravo

AF:

0.408

Asia WGS

AF:

0.497

AC:

1726

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.62

(source)

DANN

Benign

0.65

PhyloP100

-0.18

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