rs604459

chr22-26307622-G-A

Variant summary

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

The NM_021115.5(SEZ6L):c.1514+1478G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 151,954 control chromosomes in the GnomAD database, including 17,228 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 0.46 (17228 hom., cov: 31)
• Consequence: SEZ6L NM_021115.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.38

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.614 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEZ6L	NM_021115.5	c.1514+1478G>A		intron_variant		ENST00000248933.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEZ6L	ENST00000248933.11	c.1514+1478G>A		intron_variant		1	NM_021115.5	P4

Frequencies

GnomAD3 genomes AF: 0.458 AC: 69577 AN: 151838 Hom.: 17210 Cov.: 31

Gnomad AFR AF: 0.620

Gnomad AMI AF: 0.559

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.455

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.187

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.438

Gnomad OTH AF: 0.450

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

GnomAD4 genome AF: 0.458 AC: 69640 AN: 151954 Hom.: 17228 Cov.: 31 AF XY: 0.449 AC XY: 33317 AN XY: 74250

Gnomad4 AFR AF: 0.620

Gnomad4 AMR AF: 0.364

Gnomad4 ASJ AF: 0.455

Gnomad4 EAS AF: 0.106

Gnomad4 SAS AF: 0.186

Gnomad4 FIN AF: 0.384

Gnomad4 NFE AF: 0.438

Gnomad4 OTH AF: 0.445

Alfa AF: 0.468 Hom.: 3303

Bravo AF: 0.469

Asia WGS AF: 0.204 AC: 708 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.055
Dann	Benign	0.50

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: rs604459; hg19: chr22-26703588;