chr5-42844019-T-A

Variant names:

• chr5-42844019-T-A
• rs7719242
• ENST00000514218.5:c.-13-35653A>T

Variant summary

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

The ENST00000651306.1(ENSG00000286271):​n.377+26668T>A variant causes a intron 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: ENSG00000286271 ENST00000651306.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.421
• Publications: 6 publications found

Genes affected

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]

ENSG00000286271 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000651306.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SELENOP	ENST00000514218.5	TSL:5	c.-13-35653A>T		intron	N/A	ENSP00000421626.1	A0A182DWH7
	ENSG00000286271	ENST00000651306.1		n.377+26668T>A		intron	N/A
	ENSG00000286271	ENST00000653383.1		n.273+30100T>A		intron	N/A

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

African (AFR) AF: 0.144 AC: 5978 AN: 41532

American (AMR) AF: 0.347 AC: 5302 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 814 AN: 3468

East Asian (EAS) AF: 0.277 AC: 1431 AN: 5168

South Asian (SAS) AF: 0.254 AC: 1221 AN: 4814

European-Finnish (FIN) AF: 0.286 AC: 3019 AN: 10574

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.240 AC: 16284 AN: 67986

Other (OTH) AF: 0.223 AC: 471 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.9
DANN	Benign	0.63
PhyloP100		-0.42

Splicing

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

Other links and lift over

dbSNP: rs7719242; hg19: chr5-42844121;