rs13090569

chr3-167753757-G-A

Variant summary

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

The NM_001122752.2(SERPINI1):c.-19+17934G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 152,032 control chromosomes in the GnomAD database, including 9,551 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 0.33 (9551 hom., cov: 32)
• Consequence: SERPINI1 NM_001122752.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.880

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=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERPINI1	NM_001122752.2	c.-19+17934G>A		intron_variant		ENST00000446050.7
SERPINI1	NM_005025.5	c.-19+17622G>A		intron_variant
SERPINI1	XM_017006618.3	c.-19+17945G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINI1	ENST00000446050.7	c.-19+17934G>A		intron_variant		1	NM_001122752.2	P1
SERPINI1	ENST00000295777.9	c.-19+17622G>A		intron_variant		1		P1
SERPINI1	ENST00000472747.2	c.-19+17945G>A		intron_variant		3
SERPINI1	ENST00000472941.5	c.-19+18432G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50456 AN: 151914 Hom.: 9525 Cov.: 32

Gnomad AFR AF: 0.528

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.182

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.296

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

GnomAD4 genome AF: 0.332 AC: 50524 AN: 152032 Hom.: 9551 Cov.: 32 AF XY: 0.329 AC XY: 24466 AN XY: 74306

Gnomad4 AFR AF: 0.528

Gnomad4 AMR AF: 0.240

Gnomad4 ASJ AF: 0.133

Gnomad4 EAS AF: 0.268

Gnomad4 SAS AF: 0.116

Gnomad4 FIN AF: 0.344

Gnomad4 NFE AF: 0.266

Gnomad4 OTH AF: 0.295

Alfa AF: 0.310 Hom.: 1339

Bravo AF: 0.337

Asia WGS AF: 0.216 AC: 751 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	11
Dann	Benign	0.73

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: rs13090569; hg19: chr3-167471545;