rs2092201

chr22-26184509-C-T

Variant summary

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

The NM_021115.5(SEZ6L):c.94+14746C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0486 in 152,268 control chromosomes in the GnomAD database, including 344 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 0.049 (344 hom., cov: 32)
• Consequence: SEZ6L NM_021115.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0560

Genes affected

SEZ6L (HGNC:10763): (seizure related 6 homolog like) Predicted to act upstream of or within adult locomotory behavior; nervous system development; and regulation of protein kinase C signaling. Predicted to be located in endoplasmic reticulum and neuronal cell body. [provided by Alliance of Genome Resources, Apr 2022]

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 = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEZ6L	NM_021115.5	c.94+14746C>T		intron_variant		ENST00000248933.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEZ6L	ENST00000248933.11	c.94+14746C>T		intron_variant		1	NM_021115.5	P4

Frequencies

GnomAD3 genomes AF: 0.0487 AC: 7404 AN: 152148 Hom.: 345 Cov.: 32

Gnomad AFR AF: 0.00958

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.0490

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.0793

Gnomad FIN AF: 0.0447

Gnomad MID AF: 0.0159

Gnomad NFE AF: 0.0459

Gnomad OTH AF: 0.0609

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

GnomAD4 genome AF: 0.0486 AC: 7405 AN: 152268 Hom.: 344 Cov.: 32 AF XY: 0.0521 AC XY: 3878 AN XY: 74438

Gnomad4 AFR AF: 0.00957

Gnomad4 AMR AF: 0.103

Gnomad4 ASJ AF: 0.0490

Gnomad4 EAS AF: 0.216

Gnomad4 SAS AF: 0.0795

Gnomad4 FIN AF: 0.0447

Gnomad4 NFE AF: 0.0459

Gnomad4 OTH AF: 0.0593

Alfa AF: 0.0491 Hom.: 510

Bravo AF: 0.0537

Asia WGS AF: 0.136 AC: 471 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	4.2
Dann	Benign	0.76

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: rs2092201; hg19: chr22-26580475;