rs3216411

Positions:

• chr22-30417563-T-TG
• chr22-30417563-T-TGG

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_012429.5(SEC14L2):​c.1081+1164dupG variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.74 (42315 hom., cov: 0)
• Consequence: SEC14L2 NM_012429.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.623

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

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.857 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEC14L2	NM_012429.5	c.1081+1164dupG		intron_variant		ENST00000615189.5	NP_036561.1
SEC14L2	NM_001291932.2	c.919+1164dupG		intron_variant			NP_001278861.1
SEC14L2	NM_001204204.3	c.832+1164dupG		intron_variant			NP_001191133.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEC14L2	ENST00000615189.5	c.1081+1164dupG		intron_variant		1	NM_012429.5	ENSP00000478755.1
ENSG00000249590	ENST00000439838.5	c.583+1164dupG		intron_variant		2		ENSP00000415178.1

Frequencies

GnomAD3 genomes AF: 0.744 AC: 113089 AN: 151932 Hom.: 42279 Cov.: 0

Gnomad AFR AF: 0.754

Gnomad AMI AF: 0.648

Gnomad AMR AF: 0.777

Gnomad ASJ AF: 0.765

Gnomad EAS AF: 0.872

Gnomad SAS AF: 0.880

Gnomad FIN AF: 0.768

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.708

Gnomad OTH AF: 0.757

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

GnomAD4 genome AF: 0.744 AC: 113176 AN: 152048 Hom.: 42315 Cov.: 0 AF XY: 0.752 AC XY: 55927 AN XY: 74330

Gnomad4 AFR AF: 0.754

Gnomad4 AMR AF: 0.776

Gnomad4 ASJ AF: 0.765

Gnomad4 EAS AF: 0.873

Gnomad4 SAS AF: 0.879

Gnomad4 FIN AF: 0.768

Gnomad4 NFE AF: 0.708

Gnomad4 OTH AF: 0.759

Alfa AF: 0.711 Hom.: 4680

Bravo AF: 0.739

Asia WGS AF: 0.877 AC: 3048 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs3216411; hg19: chr22-30813552;