rs2055028

Variant names:

• chr3-167812718-G-A
• rs2055028
• NM_001122752.2:c.979+5377G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-167812718-G-A
• chr3-167812718-G-T

Variant summary

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

The NM_001122752.2(SERPINI1):​c.979+5377G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.813 in 152,180 control chromosomes in the GnomAD database, including 50,545 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 0.81 (50545 hom., cov: 32)
• Consequence: SERPINI1 NM_001122752.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.267
• Publications: 3 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, 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.946 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINI1	NM_001122752.2	c.979+5377G>A		intron_variant	Intron 6 of 8	ENST00000446050.7	NP_001116224.1
SERPINI1	NM_005025.5	c.979+5377G>A		intron_variant	Intron 6 of 8		NP_005016.1
SERPINI1	XM_017006618.3	c.979+5377G>A		intron_variant	Intron 6 of 8		XP_016862107.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINI1	ENST00000446050.7	c.979+5377G>A		intron_variant	Intron 6 of 8	1	NM_001122752.2	ENSP00000397373.2
SERPINI1	ENST00000295777.9	c.979+5377G>A		intron_variant	Intron 6 of 8	1		ENSP00000295777.5
SERPINI1	ENST00000466865.1	c.103+5377G>A		intron_variant	Intron 1 of 3	2		ENSP00000420807.1
SERPINI1	ENST00000488374.5	n.175+5377G>A		intron_variant	Intron 2 of 4	3

Frequencies

GnomAD3 genomes AF: 0.813 AC: 123658 AN: 152062 Hom.: 50505 Cov.: 32

Gnomad AFR AF: 0.752

Gnomad AMI AF: 0.765

Gnomad AMR AF: 0.877

Gnomad ASJ AF: 0.784

Gnomad EAS AF: 0.968

Gnomad SAS AF: 0.861

Gnomad FIN AF: 0.809

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.823

Gnomad OTH AF: 0.836

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

GnomAD4 genome AF: 0.813 AC: 123752 AN: 152180 Hom.: 50545 Cov.: 32 AF XY: 0.814 AC XY: 60560 AN XY: 74384

African (AFR) AF: 0.752 AC: 31200 AN: 41492

American (AMR) AF: 0.877 AC: 13418 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.784 AC: 2721 AN: 3472

East Asian (EAS) AF: 0.968 AC: 5024 AN: 5188

South Asian (SAS) AF: 0.861 AC: 4152 AN: 4820

European-Finnish (FIN) AF: 0.809 AC: 8558 AN: 10582

Middle Eastern (MID) AF: 0.820 AC: 241 AN: 294

European-Non Finnish (NFE) AF: 0.823 AC: 55971 AN: 68012

Other (OTH) AF: 0.838 AC: 1769 AN: 2112

Alfa AF: 0.809 Hom.: 4590

Bravo AF: 0.816

Asia WGS AF: 0.893 AC: 3105 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.27
PhyloP100		-0.27
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: rs2055028; hg19: chr3-167530506;