rs1010324

Variant names:

• chr22-30399900-G-A
• rs1010324
• NM_012429.5:c.130+182G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012429.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC14L2	NM_012429.5	MANE Select	c.130+182G>A		intron	N/A	NP_036561.1	O76054-1
	SEC14L2	NM_033382.3		c.130+182G>A		intron	N/A	NP_203740.1	O76054-4
	SEC14L2	NM_001291932.2		c.-33+2730G>A		intron	N/A	NP_001278861.1	B7Z3Z8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC14L2	ENST00000615189.5	TSL:1 MANE Select	c.130+182G>A		intron	N/A	ENSP00000478755.1	O76054-1
	SEC14L2	ENST00000405717.7	TSL:1	c.130+182G>A		intron	N/A	ENSP00000385186.3	O76054-4
	SEC14L2	ENST00000464335.5	TSL:1	n.35+182G>A		intron	N/A

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

African (AFR) AF: 0.0381 AC: 1583 AN: 41576

American (AMR) AF: 0.221 AC: 3379 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 746 AN: 3472

East Asian (EAS) AF: 0.359 AC: 1861 AN: 5180

South Asian (SAS) AF: 0.390 AC: 1881 AN: 4822

European-Finnish (FIN) AF: 0.204 AC: 2166 AN: 10608

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.176 AC: 11948 AN: 68014

Other (OTH) AF: 0.158 AC: 334 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	21
DANN	Benign	0.82
PhyloP100		3.0
Mutation Taster		=99/1	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: rs1010324; hg19: chr22-30795889; COSMIC: COSV57241318;