rs2387591

Positions:

• chr19-49048586-A-C
• chr19-49048586-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_033183.3(CGB8):​c.15+139T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00132 in 1,596,764 control chromosomes in the GnomAD database, including 25 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 0.0080 (11 hom., cov: 32)
  • Exomes 𝑓: 0.00063 (14 hom.)
• Consequence: CGB8 NM_033183.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.63

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=-0.99).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00796 (1190/149444) while in subpopulation AFR AF= 0.0284 (1109/39054). AF 95% confidence interval is 0.027. There are 11 homozygotes in gnomad4. There are 568 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CGB8	NM_033183.3	c.15+139T>G		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+139T>G		intron_variant		1	NM_033183.3	ENSP00000403649	P1

Frequencies

GnomAD3 genomes AF: 0.00796 AC: 1189 AN: 149336 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.0285

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00316

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000416

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000324

Gnomad OTH AF: 0.00436

GnomAD4 exome AF: 0.000631 AC: 913 AN: 1447320 Hom.: 14 AF XY: 0.000549 AC XY: 395 AN XY: 719014

Gnomad4 AFR exome AF: 0.0176

Gnomad4 AMR exome AF: 0.00137

Gnomad4 ASJ exome AF: 0.0000395

Gnomad4 EAS exome AF: 0.000354

Gnomad4 SAS exome AF: 0.000283

Gnomad4 FIN exome AF: 0.0000567

Gnomad4 NFE exome AF: 0.000165

Gnomad4 OTH exome AF: 0.00128

GnomAD4 genome AF: 0.00796 AC: 1190 AN: 149444 Hom.: 11 Cov.: 32 AF XY: 0.00777 AC XY: 568 AN XY: 73108

Gnomad4 AFR AF: 0.0284

Gnomad4 AMR AF: 0.00316

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000417

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000324

Gnomad4 OTH AF: 0.00431

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.1
DANN	Benign	0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs2387591; hg19: chr19-49551843;