NM_012429.5:c.1081+931A>G

Variant names:

• chr22-30417334-A-G
• rs2299825
• NM_012429.5:c.1081+931A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012429.5(SEC14L2):​c.1081+931A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 152,232 control chromosomes in the GnomAD database, including 2,843 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 0.18 (2843 hom., cov: 33)
• Consequence: SEC14L2 NM_012429.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.131
• Publications: 9 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]

ENSG00000249590 (HGNC:):

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.223 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC14L2	NM_012429.5	MANE Select	c.1081+931A>G		intron	N/A	NP_036561.1
	SEC14L2	NM_001291932.2		c.919+931A>G		intron	N/A	NP_001278861.1
	SEC14L2	NM_001204204.3		c.832+931A>G		intron	N/A	NP_001191133.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC14L2	ENST00000615189.5	TSL:1 MANE Select	c.1081+931A>G		intron	N/A	ENSP00000478755.1
	ENSG00000249590	ENST00000439838.5	TSL:2	c.583+931A>G		intron	N/A	ENSP00000415178.1
	SEC14L2	ENST00000619483.4	TSL:1	n.1176+931A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28151 AN: 152112 Hom.: 2842 Cov.: 33

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.0996

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.306

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.236

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

GnomAD4 genome AF: 0.185 AC: 28149 AN: 152232 Hom.: 2843 Cov.: 33 AF XY: 0.180 AC XY: 13381 AN XY: 74418

African (AFR) AF: 0.127 AC: 5265 AN: 41530

American (AMR) AF: 0.190 AC: 2903 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.310 AC: 1075 AN: 3472

East Asian (EAS) AF: 0.135 AC: 701 AN: 5184

South Asian (SAS) AF: 0.0988 AC: 477 AN: 4828

European-Finnish (FIN) AF: 0.160 AC: 1692 AN: 10588

Middle Eastern (MID) AF: 0.312 AC: 91 AN: 292

European-Non Finnish (NFE) AF: 0.226 AC: 15350 AN: 68020

Other (OTH) AF: 0.232 AC: 491 AN: 2114

Alfa AF: 0.217 Hom.: 3129

Bravo AF: 0.188

Asia WGS AF: 0.130 AC: 454 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	8.2
DANN	Benign	0.87
PhyloP100		0.13
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: rs2299825; hg19: chr22-30813323;