rs2420034

Variant names:

• chr3-167737217-T-A
• rs2420034
• NM_001122752.2:c.-19+1394T>A

Your query was ambiguous. Multiple possible variants found:

• chr3-167737217-T-A
• chr3-167737217-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001122752.2(SERPINI1):​c.-19+1394T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 151,888 control chromosomes in the GnomAD database, including 26,487 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 0.56 (26487 hom., cov: 31)
• Consequence: SERPINI1 NM_001122752.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.257
• Publications: 4 publications found

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, PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.84 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001122752.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINI1	NM_001122752.2	MANE Select	c.-19+1394T>A		intron	N/A	NP_001116224.1	A0A0S2Z455
	SERPINI1	NM_005025.5		c.-19+1082T>A		intron	N/A	NP_005016.1	A0A0S2Z455

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINI1	ENST00000446050.7	TSL:1 MANE Select	c.-19+1394T>A		intron	N/A	ENSP00000397373.2	Q99574
	SERPINI1	ENST00000295777.9	TSL:1	c.-19+1082T>A		intron	N/A	ENSP00000295777.5	Q99574
	SERPINI1	ENST00000872947.1		c.-19+2047T>A		intron	N/A	ENSP00000543006.1

Frequencies

GnomAD3 genomes AF: 0.559 AC: 84777 AN: 151770 Hom.: 26431 Cov.: 31

Gnomad AFR AF: 0.847

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.343

Gnomad EAS AF: 0.350

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.531

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.480

Gnomad OTH AF: 0.463

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

GnomAD4 genome AF: 0.559 AC: 84872 AN: 151888 Hom.: 26487 Cov.: 31 AF XY: 0.550 AC XY: 40848 AN XY: 74214

African (AFR) AF: 0.847 AC: 35114 AN: 41458

American (AMR) AF: 0.359 AC: 5478 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.343 AC: 1186 AN: 3460

East Asian (EAS) AF: 0.349 AC: 1801 AN: 5166

South Asian (SAS) AF: 0.350 AC: 1681 AN: 4806

European-Finnish (FIN) AF: 0.531 AC: 5587 AN: 10524

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.480 AC: 32556 AN: 67874

Other (OTH) AF: 0.461 AC: 975 AN: 2116

Alfa AF: 0.528 Hom.: 2716

Bravo AF: 0.557

Asia WGS AF: 0.392 AC: 1364 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.92
DANN	Benign	0.56
PhyloP100		-0.26
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2420034; hg19: chr3-167455005;