rs13345685

Positions:

• chr19-49049004-G-A
• chr19-49049004-G-C

Variant summary

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

The NM_033183.3(CGB8):​c.-265C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 1,351,002 control chromosomes in the GnomAD database, including 62,100 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 0.32 (7810 hom., cov: 30)
  • Exomes 𝑓: 0.30 (54290 hom.)
• Consequence: CGB8 NM_033183.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.235

Genes affected

CGB8 (HGNC:16453): (chorionic gonadotropin subunit beta 8) This gene is a member of the glycoprotein hormone beta chain family and encodes the beta 8 subunit of chorionic gonadotropin (CG). Glycoprotein hormones are heterodimers consisting of a common alpha subunit and an unique beta subunit which confers biological specificity. CG is produced by the trophoblastic cells of the placenta and stimulates the ovaries to synthesize the steroids that are essential for the maintenance of pregnancy. The beta subunit of CG is encoded by 6 genes which are arranged in tandem and inverted pairs on chromosome 19q13.3 and contiguous with the luteinizing hormone beta subunit gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CGB8	NM_033183.3	c.-265C>T		5_prime_UTR_variant	1/3	ENST00000448456.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CGB8	ENST00000448456.4	c.-265C>T		5_prime_UTR_variant	1/3	1	NM_033183.3	P1

Frequencies

GnomAD3 genomes AF: 0.324 AC: 48783 AN: 150504 Hom.: 7811 Cov.: 30

Gnomad AFR AF: 0.337

Gnomad AMI AF: 0.410

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.316

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.327

GnomAD4 exome AF: 0.303 AC: 363768 AN: 1200374 Hom.: 54290 Cov.: 21 AF XY: 0.304 AC XY: 176758 AN XY: 580934

Gnomad4 AFR exome AF: 0.341

Gnomad4 AMR exome AF: 0.280

Gnomad4 ASJ exome AF: 0.291

Gnomad4 EAS exome AF: 0.319

Gnomad4 SAS exome AF: 0.321

Gnomad4 FIN exome AF: 0.386

Gnomad4 NFE exome AF: 0.297

Gnomad4 OTH exome AF: 0.321

GnomAD4 genome AF: 0.324 AC: 48793 AN: 150628 Hom.: 7810 Cov.: 30 AF XY: 0.326 AC XY: 23989 AN XY: 73572

Gnomad4 AFR AF: 0.337

Gnomad4 AMR AF: 0.290

Gnomad4 ASJ AF: 0.292

Gnomad4 EAS AF: 0.316

Gnomad4 SAS AF: 0.310

Gnomad4 FIN AF: 0.386

Gnomad4 NFE AF: 0.316

Gnomad4 OTH AF: 0.323

Alfa AF: 0.197 Hom.: 388

Bravo AF: 0.317

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.89
DANN	Benign	0.44

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: rs13345685; hg19: chr19-49552261; COSMIC: COSV56822926; COSMIC: COSV56822926;