22-30406040-C-G

Position:

• chr22-30406040-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012429.5(SEC14L2):​c.131-302C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.745 in 151,708 control chromosomes in the GnomAD database, including 42,296 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 0.75 (42296 hom., cov: 28)
• Consequence: SEC14L2 NM_012429.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00100

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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.856 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEC14L2	NM_012429.5	c.131-302C>G		intron_variant		ENST00000615189.5
SEC14L2	NM_001204204.3	c.131-302C>G		intron_variant
SEC14L2	NM_001291932.2	c.-32-302C>G		intron_variant
SEC14L2	NM_033382.3	c.131-302C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEC14L2	ENST00000615189.5	c.131-302C>G		intron_variant		1	NM_012429.5	P1

Frequencies

GnomAD3 genomes AF: 0.745 AC: 112941 AN: 151590 Hom.: 42257 Cov.: 28

Gnomad AFR AF: 0.756

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: 0.769

Gnomad MID AF: 0.840

Gnomad NFE AF: 0.708

Gnomad OTH AF: 0.758

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

GnomAD4 genome AF: 0.745 AC: 113033 AN: 151708 Hom.: 42296 Cov.: 28 AF XY: 0.753 AC XY: 55844 AN XY: 74136

Gnomad4 AFR AF: 0.756

Gnomad4 AMR AF: 0.777

Gnomad4 ASJ AF: 0.765

Gnomad4 EAS AF: 0.873

Gnomad4 SAS AF: 0.878

Gnomad4 FIN AF: 0.769

Gnomad4 NFE AF: 0.708

Gnomad4 OTH AF: 0.761

Alfa AF: 0.611 Hom.: 1672

Bravo AF: 0.741

Asia WGS AF: 0.878 AC: 3052 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.2
DANN	Benign	0.40

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: rs737723; hg19: chr22-30802029;