rs16872762

Variant names:

• chr5-42799823-A-G
• rs16872762
• NM_001134848.2:c.*42A>G

Variant summary

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

The NM_001134848.2(CCDC152):​c.*42A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0216 in 1,543,092 control chromosomes in the GnomAD database, including 1,734 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 0.018 (143 hom., cov: 33)
  • Exomes 𝑓: 0.022 (1591 hom.)
• Consequence: CCDC152 NM_001134848.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.457

Genes affected

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

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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC152	NM_001134848.2	c.*42A>G		3_prime_UTR_variant	Exon 9 of 9	ENST00000361970.10	NP_001128320.1
SELENOP	NM_005410.4	c.*897T>C		downstream_gene_variant		ENST00000514985.6	NP_005401.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC152	ENST00000361970.10	c.*42A>G		3_prime_UTR_variant	Exon 9 of 9	1	NM_001134848.2	ENSP00000354888.5
CCDC152	ENST00000388827.4	c.*42A>G		3_prime_UTR_variant	Exon 7 of 7	2		ENSP00000373479.4
SELENOP	ENST00000514985.6	c.*897T>C		downstream_gene_variant		1	NM_005410.4	ENSP00000420939.1
SELENOP	ENST00000512980.5	n.*60T>C		downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.0179 AC: 2726 AN: 152220 Hom.: 143 Cov.: 33

Gnomad AFR AF: 0.00429

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0166

Gnomad ASJ AF: 0.00893

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.00367

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.00904

Gnomad OTH AF: 0.0182

GnomAD3 exomes AF: 0.0432 AC: 6434 AN: 149048 Hom.: 479 AF XY: 0.0513 AC XY: 4045 AN XY: 78840

Gnomad AFR exome AF: 0.00399

Gnomad AMR exome AF: 0.0252

Gnomad ASJ exome AF: 0.0105

Gnomad EAS exome AF: 0.136

Gnomad SAS exome AF: 0.173

Gnomad FIN exome AF: 0.00310

Gnomad NFE exome AF: 0.0101

Gnomad OTH exome AF: 0.0270

GnomAD4 exome AF: 0.0220 AC: 30655 AN: 1390754 Hom.: 1591 Cov.: 30 AF XY: 0.0262 AC XY: 17998 AN XY: 685648

Gnomad4 AFR exome AF: 0.00338

Gnomad4 AMR exome AF: 0.0247

Gnomad4 ASJ exome AF: 0.0102

Gnomad4 EAS exome AF: 0.0959

Gnomad4 SAS exome AF: 0.169

Gnomad4 FIN exome AF: 0.00289

Gnomad4 NFE exome AF: 0.0101

Gnomad4 OTH exome AF: 0.0312

GnomAD4 genome AF: 0.0179 AC: 2729 AN: 152338 Hom.: 143 Cov.: 33 AF XY: 0.0206 AC XY: 1533 AN XY: 74488

Gnomad4 AFR AF: 0.00430

Gnomad4 AMR AF: 0.0171

Gnomad4 ASJ AF: 0.00893

Gnomad4 EAS AF: 0.136

Gnomad4 SAS AF: 0.176

Gnomad4 FIN AF: 0.00367

Gnomad4 NFE AF: 0.00904

Gnomad4 OTH AF: 0.0180

Alfa AF: 0.0133 Hom.: 13

Bravo AF: 0.0158

Asia WGS AF: 0.145 AC: 503 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.3
DANN	Benign	0.45

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

Publications

LitVar

Other links and lift over

dbSNP: rs16872762; hg19: chr5-42799925;