dbSNP rs6783981: SERPINI1:c.979+3000T>C (chr3-167810341-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001122752.2(SERPINI1):c.979+3000T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 151,844 control chromosomes in the GnomAD database, including 24,492 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 0.54 ( 24492 hom., cov: 31)

Consequence

SERPINI1
NM_001122752.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.31

Publications

10 publications found

Variant links:

Genes affected

SERPINI1 (HGNC:8943): (serpin family I member 1) This gene encodes a member of the serpin superfamily of serine proteinase inhibitors. The protein is primarily secreted by axons in the brain, and preferentially reacts with and inhibits tissue-type plasminogen activator. It is thought to play a role in the regulation of axonal growth and the development of synaptic plasticity. Mutations in this gene result in familial encephalopathy with neuroserpin inclusion bodies (FENIB), which is a dominantly inherited form of familial encephalopathy and epilepsy characterized by the accumulation of mutant neuroserpin polymers. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Jul 2008]

SERPINI1 Gene-Disease associations (from GenCC):

progressive myoclonus epilepsy
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
familial encephalopathy with neuroserpin inclusion bodies
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)

SERPINI1 links:

ENSG00000287319 (HGNC:):

ENSG00000287319 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=-0.78).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.749 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SERPINI1	NM_001122752.2 link	c.979+3000T>C	intron_variant	Intron 6 of 8	ENST00000446050.7	NP_001116224.1	Q99574A0A0S2Z455
SERPINI1	NM_005025.5 link	c.979+3000T>C	intron_variant	Intron 6 of 8		NP_005016.1	Q99574A0A0S2Z455
SERPINI1	XM_017006618.3 link	c.979+3000T>C	intron_variant	Intron 6 of 8		XP_016862107.1	Q99574A0A0S2Z455

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINI1	ENST00000446050.7 link	c.979+3000T>C		intron_variant	Intron 6 of 8	1	NM_001122752.2	ENSP00000397373.2		Q99574

Frequencies

GnomAD3 genomes

AF:

0.543

AC:

82456

AN:

151726

Hom.:

24459

Cov.:

show subpopulations

Gnomad AFR

AF:

0.756

Gnomad AMI

AF:

0.442

Gnomad AMR

AF:

0.425

Gnomad ASJ

AF:

0.472

Gnomad EAS

AF:

0.0748

Gnomad SAS

AF:

0.290

Gnomad FIN

AF:

0.468

Gnomad MID

AF:

0.430

Gnomad NFE

AF:

0.512

Gnomad OTH

AF:

0.531

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.544

AC:

82535

AN:

151844

Hom.:

24492

Cov.:

AF XY:

0.532

AC XY:

39460

AN XY:

74196

show subpopulations

African (AFR)

AF:

0.756

AC:

31321

AN:

41416

American (AMR)

AF:

0.425

AC:

6480

AN:

15244

Ashkenazi Jewish (ASJ)

AF:

0.472

AC:

1639

AN:

3470

East Asian (EAS)

AF:

0.0745

AC:

386

AN:

5178

South Asian (SAS)

AF:

0.289

AC:

1387

AN:

4806

European-Finnish (FIN)

AF:

0.468

AC:

4920

AN:

10520

Middle Eastern (MID)

AF:

0.425

AC:

124

AN:

292

European-Non Finnish (NFE)

AF:

0.512

AC:

34761

AN:

67896

Other (OTH)

AF:

0.528

AC:

1115

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1728

3456

5185

6913

8641

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

682

1364

2046

2728

3410

<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:

0.510

Hom.:

12830

Bravo

AF:

0.551

Asia WGS

AF:

0.232

AC:

806

AN:

3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

(source)

DANN

Benign

0.91

PhyloP100

1.3

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over