22-30423770-G-A

Variant names:

• chr22-30423770-G-A
• rs1061664
• ENST00000619483.4:n.2670G>A

Variant summary

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

The ENST00000615189.5(SEC14L2):​c.*1363G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 152,398 control chromosomes in the GnomAD database, including 3,179 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 0.20 (3179 hom., cov: 34)
  • Exomes 𝑓: 0.15 (0 hom.)
• Consequence: SEC14L2 ENST00000615189.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.07
• Publications: 14 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:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000615189.5. 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.*1363G>A		3_prime_UTR	Exon 12 of 12	NP_036561.1
	SEC14L2	NM_001291932.2		c.*1363G>A		3_prime_UTR	Exon 11 of 11	NP_001278861.1
	SEC14L2	NM_001204204.3		c.*1363G>A		3_prime_UTR	Exon 10 of 10	NP_001191133.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC14L2	ENST00000619483.4	TSL:1	n.2670G>A		non_coding_transcript_exon	Exon 11 of 11
	SEC14L2	ENST00000615189.5	TSL:1 MANE Select	c.*1363G>A		3_prime_UTR	Exon 12 of 12	ENSP00000478755.1
	ENSG00000249590	ENST00000439838.5	TSL:2	c.584-2947G>A		intron	N/A	ENSP00000415178.1

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29725 AN: 152208 Hom.: 3189 Cov.: 34

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.283

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.204

GnomAD4 exome AF: 0.153 AC: 11 AN: 72 Hom.: 0 Cov.: 0 AF XY: 0.190 AC XY: 8 AN XY: 42

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.250 AC: 1 AN: 4

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.145 AC: 9 AN: 62

Other (OTH) AF: 0.250 AC: 1 AN: 4

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000633684), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.195 AC: 29709 AN: 152326 Hom.: 3179 Cov.: 34 AF XY: 0.202 AC XY: 15018 AN XY: 74476

African (AFR) AF: 0.115 AC: 4787 AN: 41596

American (AMR) AF: 0.251 AC: 3842 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 600 AN: 3472

East Asian (EAS) AF: 0.284 AC: 1472 AN: 5184

South Asian (SAS) AF: 0.276 AC: 1331 AN: 4826

European-Finnish (FIN) AF: 0.249 AC: 2636 AN: 10604

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.209 AC: 14217 AN: 68018

Other (OTH) AF: 0.201 AC: 425 AN: 2114

Alfa AF: 0.201 Hom.: 5150

Bravo AF: 0.191

Asia WGS AF: 0.273 AC: 945 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	9.1
DANN	Benign	0.90
PhyloP100		1.1
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: rs1061664; hg19: chr22-30819758;