rs13090836

Positions:

• chr3-167790274-T-C
• chr3-167790274-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001122752.2(SERPINI1):​c.251-98T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 863,804 control chromosomes in the GnomAD database, including 71,012 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.45 (16122 hom., cov: 32)
  • Exomes 𝑓: 0.39 (54890 hom.)
• Consequence: SERPINI1 NM_001122752.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.492

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 3-167790274-T-C is Benign according to our data. Variant chr3-167790274-T-C is described in ClinVar as [Benign]. Clinvar id is 1230249.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.6 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERPINI1	NM_001122752.2	c.251-98T>C		intron_variant		ENST00000446050.7	NP_001116224.1
SERPINI1	NM_005025.5	c.251-98T>C		intron_variant			NP_005016.1
SERPINI1	XM_017006618.3	c.251-98T>C		intron_variant			XP_016862107.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERPINI1	ENST00000446050.7	c.251-98T>C		intron_variant		1	NM_001122752.2	ENSP00000397373	P1
SERPINI1	ENST00000295777.9	c.251-98T>C		intron_variant		1		ENSP00000295777	P1
SERPINI1	ENST00000472747.2	c.251-98T>C		intron_variant		3		ENSP00000420561
SERPINI1	ENST00000472941.5	c.251-98T>C		intron_variant		3		ENSP00000420133

Frequencies

GnomAD3 genomes AF: 0.447 AC: 67980 AN: 151924 Hom.: 16100 Cov.: 32

Gnomad AFR AF: 0.606

Gnomad AMI AF: 0.412

Gnomad AMR AF: 0.360

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.315

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.457

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.406

Gnomad OTH AF: 0.396

GnomAD4 exome AF: 0.386 AC: 274509 AN: 711762 Hom.: 54890 AF XY: 0.378 AC XY: 142270 AN XY: 376098

Gnomad4 AFR exome AF: 0.602

Gnomad4 AMR exome AF: 0.330

Gnomad4 ASJ exome AF: 0.242

Gnomad4 EAS exome AF: 0.304

Gnomad4 SAS exome AF: 0.261

Gnomad4 FIN exome AF: 0.449

Gnomad4 NFE exome AF: 0.406

Gnomad4 OTH exome AF: 0.386

GnomAD4 genome AF: 0.448 AC: 68048 AN: 152042 Hom.: 16122 Cov.: 32 AF XY: 0.442 AC XY: 32864 AN XY: 74328

Gnomad4 AFR AF: 0.607

Gnomad4 AMR AF: 0.360

Gnomad4 ASJ AF: 0.239

Gnomad4 EAS AF: 0.314

Gnomad4 SAS AF: 0.256

Gnomad4 FIN AF: 0.457

Gnomad4 NFE AF: 0.406

Gnomad4 OTH AF: 0.397

Alfa AF: 0.438 Hom.: 2395

Bravo AF: 0.449

Asia WGS AF: 0.313 AC: 1089 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 15, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.36

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: rs13090836; hg19: chr3-167508062;