5-42838454-G-A

Position:

• chr5-42838454-G-A

Variant summary

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

The ENST00000668084.2(ENSG00000286271):​n.133+24535G>A variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 152,130 control chromosomes in the GnomAD database, including 949 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 0.11 (949 hom., cov: 32)
• Consequence: ENST00000668084.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.619

Genes affected

(HGNC:):

SELENOP (HGNC:10751): (selenoprotein P) This gene encodes a selenoprotein that is predominantly expressed in the liver and secreted into the plasma. This selenoprotein is unique in that it contains multiple selenocysteine (Sec) residues per polypeptide (10 in human), and accounts for most of the selenium in plasma. It has been implicated as an extracellular antioxidant, and in the transport of selenium to extra-hepatic tissues via apolipoprotein E receptor-2 (apoER2). Mice lacking this gene exhibit neurological dysfunction, suggesting its importance in normal brain function. Sec is encoded by the UGA codon, which normally signals translation termination. The 3' UTRs of selenoprotein mRNAs contain a conserved stem-loop structure, designated the Sec insertion sequence (SECIS) element, that is necessary for the recognition of UGA as a Sec codon, rather than as a stop signal. The mRNA for this selenoprotein contains two SECIS elements. The use of alternative polyadenylation sites, one located in between the two SECIS elements, results in two populations of mRNAs containing either both (predominant) or just the upstream SECIS element (PMID:27881738). Alternatively spliced transcript variants have also been found for this gene. [provided by RefSeq, Oct 2018]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC124900970	XR_007058751.1	n.463+417G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000668084.2	n.133+24535G>A		intron_variant, non_coding_transcript_variant
SELENOP	ENST00000514218.5	c.-13-30088C>T		intron_variant		5		ENSP00000421626
	ENST00000651306.1	n.377+21103G>A		intron_variant, non_coding_transcript_variant
	ENST00000653383.1	n.273+24535G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16299 AN: 152012 Hom.: 949 Cov.: 32

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.0926

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.0191

Gnomad SAS AF: 0.0800

Gnomad FIN AF: 0.0588

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.124

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.107 AC: 16311 AN: 152130 Hom.: 949 Cov.: 32 AF XY: 0.103 AC XY: 7695 AN XY: 74368

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.0924

Gnomad4 ASJ AF: 0.184

Gnomad4 EAS AF: 0.0191

Gnomad4 SAS AF: 0.0793

Gnomad4 FIN AF: 0.0588

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.123

Alfa AF: 0.104 Hom.: 1248

Bravo AF: 0.113

Asia WGS AF: 0.0440 AC: 155 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.4
DANN	Benign	0.52

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10512806; hg19: chr5-42838556;