rs7719242

chr5-42844019-T-Achr5-42844019-T-Cchr5-42844019-T-G

Variant summary

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

The ENST00000668084.2(ENSG00000286271):n.133+30100T>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 0.228 in 152,142 control chromosomes in the GnomAD database, including 4,371 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 0.23 (4371 hom., cov: 32)
• Consequence: ENST00000668084.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.421

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.339 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000668084.2	n.133+30100T>A		intron_variant, non_coding_transcript_variant
SELENOP	ENST00000514218.5	c.-13-35653A>T		intron_variant		5
	ENST00000651306.1	n.377+26668T>A		intron_variant, non_coding_transcript_variant
	ENST00000653383.1	n.273+30100T>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34686 AN: 152024 Hom.: 4360 Cov.: 32

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.218

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

GnomAD4 genome AF: 0.228 AC: 34725 AN: 152142 Hom.: 4371 Cov.: 32 AF XY: 0.231 AC XY: 17181 AN XY: 74368

Gnomad4 AFR AF: 0.144

Gnomad4 AMR AF: 0.347

Gnomad4 ASJ AF: 0.235

Gnomad4 EAS AF: 0.277

Gnomad4 SAS AF: 0.254

Gnomad4 FIN AF: 0.286

Gnomad4 NFE AF: 0.240

Gnomad4 OTH AF: 0.223

Alfa AF: 0.116 Hom.: 199

Bravo AF: 0.229

Asia WGS AF: 0.256 AC: 891 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	2.9
Dann	Benign	0.63

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7719242; hg19: chr5-42844121;