3-167813232-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001122752.2(SERPINI1):c.979+5891C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.808 in 152,144 control chromosomes in the GnomAD database, including 49,859 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 (49859 hom., cov: 32)
• Consequence: SERPINI1 NM_001122752.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.943 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERPINI1	NM_001122752.2	c.979+5891C>T		intron_variant		ENST00000446050.7
SERPINI1	NM_005025.5	c.979+5891C>T		intron_variant
SERPINI1	XM_017006618.3	c.979+5891C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINI1	ENST00000446050.7	c.979+5891C>T		intron_variant		1	NM_001122752.2	P1
SERPINI1	ENST00000295777.9	c.979+5891C>T		intron_variant		1		P1
SERPINI1	ENST00000466865.1	c.104+5891C>T		intron_variant		2
SERPINI1	ENST00000488374.5	n.175+5891C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.808 AC: 122814 AN: 152026 Hom.: 49818 Cov.: 32

Gnomad AFR AF: 0.751

Gnomad AMI AF: 0.769

Gnomad AMR AF: 0.874

Gnomad ASJ AF: 0.782

Gnomad EAS AF: 0.966

Gnomad SAS AF: 0.859

Gnomad FIN AF: 0.808

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.813

Gnomad OTH AF: 0.832

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

GnomAD4 genome AF: 0.808 AC: 122910 AN: 152144 Hom.: 49859 Cov.: 32 AF XY: 0.809 AC XY: 60192 AN XY: 74376

Gnomad4 AFR AF: 0.750

Gnomad4 AMR AF: 0.874

Gnomad4 ASJ AF: 0.782

Gnomad4 EAS AF: 0.966

Gnomad4 SAS AF: 0.860

Gnomad4 FIN AF: 0.808

Gnomad4 NFE AF: 0.813

Gnomad4 OTH AF: 0.833

Alfa AF: 0.810 Hom.: 6201

Bravo AF: 0.811

Asia WGS AF: 0.891 AC: 3098 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.28
Dann	Benign	0.39

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

LitVar

Other links and lift over

dbSNP: rs1552746; hg19: chr3-167531020;