Variant rs113533056 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001122752.2(SERPINI1):c.881+10T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00109 in 1,611,036 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0064 ( 17 hom., cov: 32)

Exomes 𝑓: 0.00053 ( 3 hom. )

Consequence

SERPINI1
NM_001122752.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.17

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 3-167794834-T-G is Benign according to our data. Variant chr3-167794834-T-G is described in ClinVar as [Benign]. Clinvar id is 466623.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-167794834-T-G is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00642 (977/152250) while in subpopulation AFR AF= 0.0229 (952/41556). AF 95% confidence interval is 0.0217. There are 17 homozygotes in gnomad4. There are 447 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 977 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
SERPINI1	NM_001122752.2 linkuse as main transcript	c.881+10T>G	intron_variant	ENST00000446050.7	NP_001116224.1
SERPINI1	NM_005025.5 linkuse as main transcript	c.881+10T>G	intron_variant		NP_005016.1
SERPINI1	XM_017006618.3 linkuse as main transcript	c.881+10T>G	intron_variant		XP_016862107.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERPINI1	ENST00000446050.7 linkuse as main transcript	c.881+10T>G		intron_variant		1	NM_001122752.2	ENSP00000397373	P1
SERPINI1	ENST00000295777.9 linkuse as main transcript	c.881+10T>G		intron_variant		1		ENSP00000295777	P1

Frequencies

GnomAD3 genomes

AF:

0.00638

AC:

971

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0229

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00162

AC:

405

AN:

250770

Hom.:

AF XY:

0.00113

AC XY:

153

AN XY:

135530

show subpopulations

Gnomad AFR exome

AF:

0.0236

Gnomad AMR exome

AF:

0.000553

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000530

AC:

773

AN:

1458786

Hom.:

Cov.:

AF XY:

0.000459

AC XY:

333

AN XY:

725870

show subpopulations

Gnomad4 AFR exome

AF:

0.0201

Gnomad4 AMR exome

AF:

0.000561

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.00106

GnomAD4 genome

AF:

0.00642

AC:

977

AN:

152250

Hom.:

Cov.:

AF XY:

0.00600

AC XY:

447

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.0229

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00459

Hom.:

Bravo

AF:

0.00710

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Familial encephalopathy with neuroserpin inclusion bodies

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 30, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

7.5

DANN

Benign

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over