rs1010324

Positions:

• chr22-30399900-G-A

Variant summary

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

The NM_012429.5(SEC14L2):​c.130+182G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 152,286 control chromosomes in the GnomAD database, including 2,526 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 0.16 (2526 hom., cov: 32)
• Consequence: SEC14L2 NM_012429.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.05

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEC14L2	NM_012429.5	c.130+182G>A		intron_variant		ENST00000615189.5	NP_036561.1
SEC14L2	NM_001204204.3	c.130+182G>A		intron_variant			NP_001191133.1
SEC14L2	NM_001291932.2	c.-33+2730G>A		intron_variant			NP_001278861.1
SEC14L2	NM_033382.3	c.130+182G>A		intron_variant			NP_203740.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEC14L2	ENST00000615189.5	c.130+182G>A		intron_variant		1	NM_012429.5	ENSP00000478755	P1

Frequencies

GnomAD3 genomes AF: 0.158 AC: 24050 AN: 152166 Hom.: 2526 Cov.: 32

Gnomad AFR AF: 0.0382

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.389

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.159

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

GnomAD4 genome AF: 0.158 AC: 24055 AN: 152286 Hom.: 2526 Cov.: 32 AF XY: 0.166 AC XY: 12351 AN XY: 74454

Gnomad4 AFR AF: 0.0381

Gnomad4 AMR AF: 0.221

Gnomad4 ASJ AF: 0.215

Gnomad4 EAS AF: 0.359

Gnomad4 SAS AF: 0.390

Gnomad4 FIN AF: 0.204

Gnomad4 NFE AF: 0.176

Gnomad4 OTH AF: 0.158

Alfa AF: 0.163 Hom.: 294

Bravo AF: 0.152

Asia WGS AF: 0.319 AC: 1112 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	21
DANN	Benign	0.82

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: rs1010324; hg19: chr22-30795889; COSMIC: COSV57241318;