22-30406040-C-G

Variant names:

• chr22-30406040-C-G
• rs737723
• NM_012429.5:c.131-302C>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.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
• 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]

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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.856 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.131-302C>G		intron	N/A	NP_036561.1
	SEC14L2	NM_033382.3		c.131-302C>G		intron	N/A	NP_203740.1
	SEC14L2	NM_001291932.2		c.-32-302C>G		intron	N/A	NP_001278861.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC14L2	ENST00000615189.5	TSL:1 MANE Select	c.131-302C>G		intron	N/A	ENSP00000478755.1
	SEC14L2	ENST00000405717.7	TSL:1	c.131-302C>G		intron	N/A	ENSP00000385186.3
	SEC14L2	ENST00000464335.5	TSL:1	n.36-302C>G		intron	N/A

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

African (AFR) AF: 0.756 AC: 31241 AN: 41320

American (AMR) AF: 0.777 AC: 11833 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.765 AC: 2647 AN: 3460

East Asian (EAS) AF: 0.873 AC: 4485 AN: 5140

South Asian (SAS) AF: 0.878 AC: 4222 AN: 4806

European-Finnish (FIN) AF: 0.769 AC: 8098 AN: 10524

Middle Eastern (MID) AF: 0.834 AC: 242 AN: 290

European-Non Finnish (NFE) AF: 0.708 AC: 48070 AN: 67918

Other (OTH) AF: 0.761 AC: 1604 AN: 2108

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.2
DANN	Benign	0.40
PhyloP100		0.0010
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: rs737723; hg19: chr22-30802029;