22-30423640-T-C

Variant names:

• chr22-30423640-T-C
• rs1061660
• ENST00000619483.4:n.2540T>C

Variant summary

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

The ENST00000619483.4(SEC14L2):​n.2540T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 152,386 control chromosomes in the GnomAD database, including 7,770 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 0.32 (7758 hom., cov: 34)
  • Exomes 𝑓: 0.33 (12 hom.)
• Consequence: SEC14L2 ENST00000619483.4 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11
• Publications: 17 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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000619483.4. 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.*1233T>C		3_prime_UTR	Exon 12 of 12	NP_036561.1
	SEC14L2	NM_001291932.2		c.*1233T>C		3_prime_UTR	Exon 11 of 11	NP_001278861.1
	SEC14L2	NM_001204204.3		c.*1233T>C		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.2540T>C		non_coding_transcript_exon	Exon 11 of 11
	SEC14L2	ENST00000615189.5	TSL:1 MANE Select	c.*1233T>C		3_prime_UTR	Exon 12 of 12	ENSP00000478755.1
	ENSG00000249590	ENST00000439838.5	TSL:2	c.584-3077T>C		intron	N/A	ENSP00000415178.1

Frequencies

GnomAD3 genomes AF: 0.317 AC: 48172 AN: 152102 Hom.: 7753 Cov.: 34

Gnomad AFR AF: 0.328

Gnomad AMI AF: 0.423

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.376

Gnomad SAS AF: 0.354

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.297

Gnomad OTH AF: 0.308

GnomAD4 exome AF: 0.331 AC: 55 AN: 166 Hom.: 12 Cov.: 0 AF XY: 0.343 AC XY: 46 AN XY: 134

African (AFR) AF: 1.00 AC: 2 AN: 2

American (AMR) AF: 0.500 AC: 1 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 1.00 AC: 2 AN: 2

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

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.313 AC: 47 AN: 150

Other (OTH) AF: 0.500 AC: 2 AN: 4

GnomAD4 genome AF: 0.317 AC: 48213 AN: 152220 Hom.: 7758 Cov.: 34 AF XY: 0.321 AC XY: 23911 AN XY: 74426

African (AFR) AF: 0.327 AC: 13601 AN: 41544

American (AMR) AF: 0.338 AC: 5177 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 805 AN: 3470

East Asian (EAS) AF: 0.376 AC: 1945 AN: 5172

South Asian (SAS) AF: 0.353 AC: 1706 AN: 4832

European-Finnish (FIN) AF: 0.343 AC: 3639 AN: 10600

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.297 AC: 20197 AN: 67980

Other (OTH) AF: 0.315 AC: 667 AN: 2116

Alfa AF: 0.297 Hom.: 9414

Bravo AF: 0.313

Asia WGS AF: 0.398 AC: 1379 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.3
DANN	Benign	0.73
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: rs1061660; hg19: chr22-30819628;