rs4787483

Positions:

• chr16-29874126-A-G

Variant summary

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

The NM_001243332.2(SEZ6L2):​c.2105-397T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 152,130 control chromosomes in the GnomAD database, including 5,122 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 0.24 (5122 hom., cov: 32)
• Consequence: SEZ6L2 NM_001243332.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0160

Genes affected

SEZ6L2 (HGNC:30844): (seizure related 6 homolog like 2) This gene encodes a seizure-related protein that is localized on the cell surface. The gene is located in a region of chromosome 16p11.2 that is thought to contain candidate genes for autism spectrum disorders (ASD), though there is no evidence directly implicating this gene in ASD. Increased expression of this gene has been found in lung cancers, and the protein is therefore considered to be a novel prognostic marker for lung cancer. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Aug 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.33 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEZ6L2	NM_001243332.2	c.2105-397T>C		intron_variant		ENST00000617533.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEZ6L2	ENST00000617533.5	c.2105-397T>C		intron_variant		1	NM_001243332.2	P1

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35910 AN: 152012 Hom.: 5121 Cov.: 32

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.0424

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.214

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

GnomAD4 genome AF: 0.236 AC: 35924 AN: 152130 Hom.: 5122 Cov.: 32 AF XY: 0.234 AC XY: 17400 AN XY: 74380

Gnomad4 AFR AF: 0.103

Gnomad4 AMR AF: 0.176

Gnomad4 ASJ AF: 0.243

Gnomad4 EAS AF: 0.0425

Gnomad4 SAS AF: 0.180

Gnomad4 FIN AF: 0.345

Gnomad4 NFE AF: 0.333

Gnomad4 OTH AF: 0.211

Alfa AF: 0.307 Hom.: 13076

Bravo AF: 0.215

Asia WGS AF: 0.0960 AC: 334 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.3
DANN	Benign	0.28

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: rs4787483; hg19: chr16-29885447;