rs13345575

Positions:

• chr19-49048571-C-G
• chr19-49048571-C-T

Variant summary

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

The NM_033183.3(CGB8):​c.15+154G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 149,726 control chromosomes in the GnomAD database, including 1,968 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 0.29 (1968 hom., cov: 32)
• Consequence: CGB8 NM_033183.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.74

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CGB8	NM_033183.3	c.15+154G>C		intron_variant		ENST00000448456.4	NP_149439.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CGB8	ENST00000448456.4	c.15+154G>C		intron_variant		1	NM_033183.3	ENSP00000403649	P1

Frequencies

GnomAD3 genomes AF: 0.286 AC: 42744 AN: 149610 Hom.: 1970 Cov.: 32

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.268

Gnomad EAS AF: 0.282

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.325

Gnomad MID AF: 0.352

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.289

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.286 AC: 42748 AN: 149726 Hom.: 1968 Cov.: 32 AF XY: 0.287 AC XY: 21029 AN XY: 73186

Gnomad4 AFR AF: 0.306

Gnomad4 AMR AF: 0.258

Gnomad4 ASJ AF: 0.268

Gnomad4 EAS AF: 0.282

Gnomad4 SAS AF: 0.271

Gnomad4 FIN AF: 0.325

Gnomad4 NFE AF: 0.274

Gnomad4 OTH AF: 0.286

Alfa AF: 0.144 Hom.: 58

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.11
DANN	Benign	0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs13345575; hg19: chr19-49551828;