rs2299825

Positions:

• chr22-30417334-A-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.64).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEC14L2	NM_012429.5	c.1081+931A>G		intron_variant		ENST00000615189.5
SEC14L2	NM_001204204.3	c.832+931A>G		intron_variant
SEC14L2	NM_001291932.2	c.919+931A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEC14L2	ENST00000615189.5	c.1081+931A>G		intron_variant		1	NM_012429.5	P1

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

Gnomad4 AFR AF: 0.127

Gnomad4 AMR AF: 0.190

Gnomad4 ASJ AF: 0.310

Gnomad4 EAS AF: 0.135

Gnomad4 SAS AF: 0.0988

Gnomad4 FIN AF: 0.160

Gnomad4 NFE AF: 0.226

Gnomad4 OTH AF: 0.232

Alfa AF: 0.214 Hom.: 2145

Bravo AF: 0.188

Asia WGS AF: 0.130 AC: 454 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	8.2
DANN	Benign	0.87

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: rs2299825; hg19: chr22-30813323;