3-10293461-T-C

Variant summary

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

The ENST00000662597.1(GHRLOS):n.1544T>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 0.316 in 152,118 control chromosomes in the GnomAD database, including 8,267 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 (8266 hom., cov: 32)
  • Exomes 𝑓: 0.38 (1 hom.)
• Consequence: GHRLOS ENST00000662597.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.271

Genes affected

GHRLOS (HGNC:33885): (ghrelin opposite strand/antisense RNA) This gene is an antisense gene of the ghrelin/obestatin prepropeptide gene. Alternatively spliced transcript variants have been identified and they may function as non-coding regulatory RNAs. [provided by RefSeq, Jan 2013]

SEC13 (HGNC:10697): (SEC13 homolog, nuclear pore and COPII coat complex component) The protein encoded by this gene belongs to the SEC13 family of WD-repeat proteins. It is a constituent of the endoplasmic reticulum and the nuclear pore complex. It has similarity to the yeast SEC13 protein, which is required for vesicle biogenesis from endoplasmic reticulum during the transport of proteins. Multiple alternatively spliced transcript variants have been found. [provided by RefSeq, Oct 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GHRLOS	NR_024145.2			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GHRLOS	ENST00000662597.1	n.1544T>C		non_coding_transcript_exon_variant	2/2
SEC13	ENST00000492602.5	n.188-125A>G		intron_variant, non_coding_transcript_variant		3
GHRLOS	ENST00000439539.3			downstream_gene_variant		1

Frequencies

GnomAD3 genomes AF: 0.316 AC: 48018 AN: 151984 Hom.: 8256 Cov.: 32

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.439

Gnomad ASJ AF: 0.258

Gnomad EAS AF: 0.549

Gnomad SAS AF: 0.472

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.303

GnomAD4 exome AF: 0.375 AC: 6 AN: 16 Hom.: 1 Cov.: 0 AF XY: 0.250 AC XY: 2 AN XY: 8

Gnomad4 AFR exome AF: 0.500

Gnomad4 SAS exome AF: 0.167

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.316 AC: 48071 AN: 152102 Hom.: 8266 Cov.: 32 AF XY: 0.326 AC XY: 24258 AN XY: 74358

Gnomad4 AFR AF: 0.274

Gnomad4 AMR AF: 0.440

Gnomad4 ASJ AF: 0.258

Gnomad4 EAS AF: 0.548

Gnomad4 SAS AF: 0.470

Gnomad4 FIN AF: 0.370

Gnomad4 NFE AF: 0.280

Gnomad4 OTH AF: 0.304

Alfa AF: 0.291 Hom.: 9195

Bravo AF: 0.320

Asia WGS AF: 0.502 AC: 1741 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	4.3
Dann	Benign	0.70

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10490815; hg19: chr3-10335145;