22-30423640-T-C

Position:

• chr22-30423640-T-C

Variant summary

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

The NM_012429.5(SEC14L2):​c.*1233T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 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 NM_012429.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEC14L2	NM_012429.5	c.*1233T>C		3_prime_UTR_variant	12/12	ENST00000615189.5
SEC14L2	NM_001204204.3	c.*1233T>C		3_prime_UTR_variant	10/10
SEC14L2	NM_001291932.2	c.*1233T>C		3_prime_UTR_variant	11/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEC14L2	ENST00000615189.5	c.*1233T>C		3_prime_UTR_variant	12/12	1	NM_012429.5	P1
SEC14L2	ENST00000619483.4	n.2540T>C		non_coding_transcript_exon_variant	11/11	1
SEC14L2	ENST00000617837.4	c.*1233T>C		3_prime_UTR_variant	10/10	2
SEC14L2	ENST00000620251.1	n.1987T>C		non_coding_transcript_exon_variant	6/6	2

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

Gnomad4 AFR exome AF: 1.00

Gnomad4 AMR exome AF: 0.500

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.250

Gnomad4 NFE exome AF: 0.313

Gnomad4 OTH exome AF: 0.500

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

Gnomad4 AFR AF: 0.327

Gnomad4 AMR AF: 0.338

Gnomad4 ASJ AF: 0.232

Gnomad4 EAS AF: 0.376

Gnomad4 SAS AF: 0.353

Gnomad4 FIN AF: 0.343

Gnomad4 NFE AF: 0.297

Gnomad4 OTH AF: 0.315

Alfa AF: 0.298 Hom.: 8052

Bravo AF: 0.313

Asia WGS AF: 0.398 AC: 1379 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.3
DANN	Benign	0.73

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: rs1061660; hg19: chr22-30819628;