rs6775296

Variant names:

• chr3-167773112-A-G
• rs6775296
• NM_001122752.2:c.-18-15999A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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=-0.85).
• 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 rank	MANE	Protein	UniProt
SERPINI1	NM_001122752.2	c.-18-15999A>G		intron_variant	Intron 1 of 8	ENST00000446050.7	NP_001116224.1
SERPINI1	NM_005025.5	c.-18-15999A>G		intron_variant	Intron 1 of 8		NP_005016.1
SERPINI1	XM_017006618.3	c.-18-15999A>G		intron_variant	Intron 1 of 8		XP_016862107.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINI1	ENST00000446050.7	c.-18-15999A>G		intron_variant	Intron 1 of 8	1	NM_001122752.2	ENSP00000397373.2
SERPINI1	ENST00000295777.9	c.-18-15999A>G		intron_variant	Intron 1 of 8	1		ENSP00000295777.5
SERPINI1	ENST00000472747.2	c.-18-15999A>G		intron_variant	Intron 1 of 4	3		ENSP00000420561.2
SERPINI1	ENST00000472941.5	c.-18-15999A>G		intron_variant	Intron 1 of 2	3		ENSP00000420133.1

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

African (AFR) AF: 0.213 AC: 8789 AN: 41186

American (AMR) AF: 0.120 AC: 1817 AN: 15172

Ashkenazi Jewish (ASJ) AF: 0.0570 AC: 197 AN: 3458

East Asian (EAS) AF: 0.0683 AC: 352 AN: 5150

South Asian (SAS) AF: 0.0357 AC: 171 AN: 4788

European-Finnish (FIN) AF: 0.151 AC: 1577 AN: 10476

Middle Eastern (MID) AF: 0.0925 AC: 27 AN: 292

European-Non Finnish (NFE) AF: 0.0908 AC: 6159 AN: 67866

Other (OTH) AF: 0.109 AC: 228 AN: 2094

Alfa AF: 0.109 Hom.: 131

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
PhyloP100		-1.4
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: rs6775296; hg19: chr3-167490900;