chr5-42799823-A-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001134848.2. 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
	CCDC152	NM_001134848.2	MANE Select	c.*42A>G		3_prime_UTR	Exon 9 of 9	NP_001128320.1
	SELENOP	NM_005410.4	MANE Select	c.*897T>C		downstream_gene	N/A	NP_005401.3
	SELENOP	NM_001093726.3		c.*897T>C		downstream_gene	N/A	NP_001087195.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC152	ENST00000361970.10	TSL:1 MANE Select	c.*42A>G		3_prime_UTR	Exon 9 of 9	ENSP00000354888.5
	CCDC152	ENST00000388827.4	TSL:2	c.*42A>G		3_prime_UTR	Exon 7 of 7	ENSP00000373479.4
	SELENOP	ENST00000514985.6	TSL:1 MANE Select	c.*897T>C		downstream_gene	N/A	ENSP00000420939.1

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

GnomAD2 exomes AF: 0.0432 AC: 6434 AN: 149048 AF XY: 0.0513

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 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

African (AFR) AF: 0.00338 AC: 105 AN: 31032

American (AMR) AF: 0.0247 AC: 824 AN: 33352

Ashkenazi Jewish (ASJ) AF: 0.0102 AC: 255 AN: 24988

East Asian (EAS) AF: 0.0959 AC: 3415 AN: 35604

South Asian (SAS) AF: 0.169 AC: 13028 AN: 77134

European-Finnish (FIN) AF: 0.00289 AC: 142 AN: 49200

Middle Eastern (MID) AF: 0.0412 AC: 231 AN: 5608

European-Non Finnish (NFE) AF: 0.0101 AC: 10855 AN: 1076142

Other (OTH) AF: 0.0312 AC: 1800 AN: 57694

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

African (AFR) AF: 0.00430 AC: 179 AN: 41592

American (AMR) AF: 0.0171 AC: 262 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00893 AC: 31 AN: 3470

East Asian (EAS) AF: 0.136 AC: 708 AN: 5188

South Asian (SAS) AF: 0.176 AC: 848 AN: 4826

European-Finnish (FIN) AF: 0.00367 AC: 39 AN: 10616

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.00904 AC: 615 AN: 68030

Other (OTH) AF: 0.0180 AC: 38 AN: 2112

Alfa AF: 0.0131 Hom.: 13

Bravo AF: 0.0158

Asia WGS AF: 0.145 AC: 503 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.3
DANN	Benign	0.45
PhyloP100		-0.46
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: rs16872762; hg19: chr5-42799925;