rs137180

Positions:

• chr22-26269708-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_021115.5(SEZ6L):​c.95-22698G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.724 in 152,206 control chromosomes in the GnomAD database, including 41,323 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 0.72 (41323 hom., cov: 33)
• Consequence: SEZ6L NM_021115.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.291

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.919 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEZ6L	NM_021115.5	c.95-22698G>A		intron_variant		ENST00000248933.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEZ6L	ENST00000248933.11	c.95-22698G>A		intron_variant		1	NM_021115.5	P4

Frequencies

GnomAD3 genomes AF: 0.724 AC: 110080 AN: 152088 Hom.: 41267 Cov.: 33

Gnomad AFR AF: 0.926

Gnomad AMI AF: 0.648

Gnomad AMR AF: 0.670

Gnomad ASJ AF: 0.631

Gnomad EAS AF: 0.441

Gnomad SAS AF: 0.486

Gnomad FIN AF: 0.636

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.671

Gnomad OTH AF: 0.704

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

GnomAD4 genome AF: 0.724 AC: 110191 AN: 152206 Hom.: 41323 Cov.: 33 AF XY: 0.717 AC XY: 53377 AN XY: 74400

Gnomad4 AFR AF: 0.926

Gnomad4 AMR AF: 0.670

Gnomad4 ASJ AF: 0.631

Gnomad4 EAS AF: 0.441

Gnomad4 SAS AF: 0.487

Gnomad4 FIN AF: 0.636

Gnomad4 NFE AF: 0.671

Gnomad4 OTH AF: 0.698

Alfa AF: 0.678 Hom.: 28128

Bravo AF: 0.736

Asia WGS AF: 0.510 AC: 1772 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	15
DANN	Benign	0.80

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: rs137180; hg19: chr22-26665674;