rs2299826

Positions:

• chr22-30417435-C-T

Variant summary

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

The NM_012429.5(SEC14L2):​c.1081+1032C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 152,250 control chromosomes in the GnomAD database, including 1,065 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 0.11 (1065 hom., cov: 33)
• Consequence: SEC14L2 NM_012429.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.831

Genes affected

SEC14L2 (HGNC:10699): (SEC14 like lipid binding 2) This gene encodes a cytosolic protein which belongs to a family of lipid-binding proteins including Sec14p, alpha-tocopherol transfer protein, and cellular retinol-binding protein. The encoded protein stimulates squalene monooxygenase which is a downstream enzyme in the cholesterol biosynthetic pathway. Alternatively spliced transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Oct 2008]

RNF215 (HGNC:33434): (ring finger protein 215) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in Golgi to vacuole transport; protein targeting to vacuole; and ubiquitin-dependent protein catabolic process. Predicted to be integral component of membrane. Predicted to be part of Golgi transport complex. Predicted to be active in endosome; membrane; and trans-Golgi network. [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=-0.73).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEC14L2	NM_012429.5	c.1081+1032C>T		intron_variant		ENST00000615189.5	NP_036561.1
SEC14L2	NM_001204204.3	c.832+1032C>T		intron_variant			NP_001191133.1
SEC14L2	NM_001291932.2	c.919+1032C>T		intron_variant			NP_001278861.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEC14L2	ENST00000615189.5	c.1081+1032C>T		intron_variant		1	NM_012429.5	ENSP00000478755	P1

Frequencies

GnomAD3 genomes AF: 0.105 AC: 16022 AN: 152132 Hom.: 1070 Cov.: 33

Gnomad AFR AF: 0.0398

Gnomad AMI AF: 0.261

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.190

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.115

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

GnomAD4 genome AF: 0.105 AC: 16012 AN: 152250 Hom.: 1065 Cov.: 33 AF XY: 0.109 AC XY: 8116 AN XY: 74424

Gnomad4 AFR AF: 0.0396

Gnomad4 AMR AF: 0.176

Gnomad4 ASJ AF: 0.106

Gnomad4 EAS AF: 0.191

Gnomad4 SAS AF: 0.151

Gnomad4 FIN AF: 0.124

Gnomad4 NFE AF: 0.114

Gnomad4 OTH AF: 0.113

Alfa AF: 0.116 Hom.: 1731

Bravo AF: 0.106

Asia WGS AF: 0.166 AC: 575 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	1.5
DANN	Benign	0.65

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: rs2299826; hg19: chr22-30813424;