rs4987017

Variant names:

• chr5-42799902-A-G
• rs4987017
• NM_005410.4:c.*818T>C

Variant summary

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

The NM_001093726.3(SELENOP):​c.*818T>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 0.00596 in 1,110,286 control chromosomes in the GnomAD database, including 270 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 0.026 (169 hom., cov: 33)
  • Exomes 𝑓: 0.0028 (101 hom.)
• Consequence: SELENOP NM_001093726.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.823
• 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]

CCDC152 (HGNC:34438): (coiled-coil domain containing 152)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.087 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001093726.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SELENOP	NM_005410.4	MANE Select	c.*818T>C		3_prime_UTR	Exon 5 of 5	NP_005401.3
	CCDC152	NM_001134848.2	MANE Select	c.*121A>G		3_prime_UTR	Exon 9 of 9	NP_001128320.1
	SELENOP	NM_001093726.3		c.*818T>C		3_prime_UTR	Exon 6 of 6	NP_001087195.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SELENOP	ENST00000514985.6	TSL:1 MANE Select	c.*818T>C		3_prime_UTR	Exon 5 of 5	ENSP00000420939.1
	CCDC152	ENST00000361970.10	TSL:1 MANE Select	c.*121A>G		3_prime_UTR	Exon 9 of 9	ENSP00000354888.5
	CCDC152	ENST00000927601.1		c.*121A>G		3_prime_UTR	Exon 10 of 10	ENSP00000597660.1

Frequencies

GnomAD3 genomes AF: 0.0258 AC: 3932 AN: 152140 Hom.: 168 Cov.: 33

Gnomad AFR AF: 0.0896

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0101

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000426

Gnomad OTH AF: 0.0172

GnomAD4 exome AF: 0.00280 AC: 2682 AN: 958028 Hom.: 101 Cov.: 12 AF XY: 0.00241 AC XY: 1177 AN XY: 488096

African (AFR) AF: 0.0929 AC: 1963 AN: 21130

American (AMR) AF: 0.00700 AC: 157 AN: 22428

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20824

East Asian (EAS) AF: 0.00 AC: 0 AN: 33340

South Asian (SAS) AF: 0.000190 AC: 12 AN: 63128

European-Finnish (FIN) AF: 0.0000226 AC: 1 AN: 44252

Middle Eastern (MID) AF: 0.00738 AC: 24 AN: 3254

European-Non Finnish (NFE) AF: 0.000296 AC: 209 AN: 706662

Other (OTH) AF: 0.00735 AC: 316 AN: 43010

GnomAD4 genome AF: 0.0259 AC: 3936 AN: 152258 Hom.: 169 Cov.: 33 AF XY: 0.0247 AC XY: 1840 AN XY: 74456

African (AFR) AF: 0.0894 AC: 3714 AN: 41544

American (AMR) AF: 0.0101 AC: 155 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000426 AC: 29 AN: 68006

Other (OTH) AF: 0.0170 AC: 36 AN: 2112

Alfa AF: 0.0119 Hom.: 53

Bravo AF: 0.0294

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.1
DANN	Benign	0.62
PhyloP100		0.82
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4987017; hg19: chr5-42800004;