chr22-26307622-G-A

Variant names:

• chr22-26307622-G-A
• rs604459
• NM_021115.5:c.1514+1478G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021115.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEZ6L	NM_021115.5	MANE Select	c.1514+1478G>A		intron	N/A	NP_066938.2
	SEZ6L	NM_001184773.2		c.1514+1478G>A		intron	N/A	NP_001171702.1
	SEZ6L	NM_001184774.2		c.1514+1478G>A		intron	N/A	NP_001171703.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEZ6L	ENST00000248933.11	TSL:1 MANE Select	c.1514+1478G>A		intron	N/A	ENSP00000248933.6
	SEZ6L	ENST00000404234.7	TSL:1	c.1514+1478G>A		intron	N/A	ENSP00000384772.3
	SEZ6L	ENST00000629590.2	TSL:1	c.1514+1478G>A		intron	N/A	ENSP00000485720.1

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

African (AFR) AF: 0.620 AC: 25699 AN: 41432

American (AMR) AF: 0.364 AC: 5556 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.455 AC: 1578 AN: 3468

East Asian (EAS) AF: 0.106 AC: 548 AN: 5176

South Asian (SAS) AF: 0.186 AC: 895 AN: 4808

European-Finnish (FIN) AF: 0.384 AC: 4036 AN: 10524

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.438 AC: 29745 AN: 67972

Other (OTH) AF: 0.445 AC: 941 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.055
DANN	Benign	0.50
PhyloP100		-2.4
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: rs604459; hg19: chr22-26703588;