rs6775296

chr3-167773112-A-G

Variant summary

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

The NM_001122752.2(SERPINI1):c.-18-15999A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 151,390 control chromosomes in the GnomAD database, including 1,510 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 0.13 (1510 hom., cov: 30)
• Consequence: SERPINI1 NM_001122752.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERPINI1	NM_001122752.2	c.-18-15999A>G		intron_variant		ENST00000446050.7
SERPINI1	NM_005025.5	c.-18-15999A>G		intron_variant
SERPINI1	XM_017006618.3	c.-18-15999A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINI1	ENST00000446050.7	c.-18-15999A>G		intron_variant		1	NM_001122752.2	P1
SERPINI1	ENST00000295777.9	c.-18-15999A>G		intron_variant		1		P1
SERPINI1	ENST00000472747.2	c.-18-15999A>G		intron_variant		3
SERPINI1	ENST00000472941.5	c.-18-15999A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19346 AN: 151276 Hom.: 1502 Cov.: 30

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.0826

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.0570

Gnomad EAS AF: 0.0686

Gnomad SAS AF: 0.0361

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.0924

Gnomad NFE AF: 0.0908

Gnomad OTH AF: 0.107

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

GnomAD4 genome AF: 0.128 AC: 19392 AN: 151390 Hom.: 1510 Cov.: 30 AF XY: 0.128 AC XY: 9482 AN XY: 73908

Gnomad4 AFR AF: 0.213

Gnomad4 AMR AF: 0.120

Gnomad4 ASJ AF: 0.0570

Gnomad4 EAS AF: 0.0683

Gnomad4 SAS AF: 0.0357

Gnomad4 FIN AF: 0.151

Gnomad4 NFE AF: 0.0908

Gnomad4 OTH AF: 0.109

Alfa AF: 0.107 Hom.: 116

Bravo AF: 0.133

Asia WGS AF: 0.0810 AC: 281 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.83
Dann	Benign	0.48

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: rs6775296; hg19: chr3-167490900;