rs35930240

Positions:

• chr19-49048811-A-T

Variant summary

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

The ENST00000448456.4(CGB8):​c.-72T>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0353 in 1,611,774 control chromosomes in the GnomAD database, including 1,249 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 0.037 (125 hom., cov: 32)
  • Exomes 𝑓: 0.035 (1124 hom.)
• Consequence: CGB8 ENST00000448456.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.14

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=-0.97).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0372 (5623/151298) while in subpopulation AFR AF= 0.0405 (1646/40670). AF 95% confidence interval is 0.0388. There are 125 homozygotes in gnomad4. There are 2708 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 125 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CGB8	NM_033183.3	c.-72T>A		5_prime_UTR_variant	1/3	ENST00000448456.4	NP_149439.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CGB8	ENST00000448456.4	c.-72T>A		5_prime_UTR_variant	1/3	1	NM_033183.3	ENSP00000403649	P1

Frequencies

GnomAD3 genomes AF: 0.0371 AC: 5613 AN: 151180 Hom.: 124 Cov.: 32

Gnomad AFR AF: 0.0403

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.0302

Gnomad ASJ AF: 0.0265

Gnomad EAS AF: 0.00541

Gnomad SAS AF: 0.0228

Gnomad FIN AF: 0.0439

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0400

Gnomad OTH AF: 0.0342

GnomAD4 exome AF: 0.0351 AC: 51255 AN: 1460476 Hom.: 1124 Cov.: 34 AF XY: 0.0348 AC XY: 25314 AN XY: 726640

Gnomad4 AFR exome AF: 0.0411

Gnomad4 AMR exome AF: 0.0221

Gnomad4 ASJ exome AF: 0.0250

Gnomad4 EAS exome AF: 0.00350

Gnomad4 SAS exome AF: 0.0209

Gnomad4 FIN exome AF: 0.0480

Gnomad4 NFE exome AF: 0.0373

Gnomad4 OTH exome AF: 0.0342

GnomAD4 genome AF: 0.0372 AC: 5623 AN: 151298 Hom.: 125 Cov.: 32 AF XY: 0.0366 AC XY: 2708 AN XY: 73956

Gnomad4 AFR AF: 0.0405

Gnomad4 AMR AF: 0.0301

Gnomad4 ASJ AF: 0.0265

Gnomad4 EAS AF: 0.00542

Gnomad4 SAS AF: 0.0226

Gnomad4 FIN AF: 0.0439

Gnomad4 NFE AF: 0.0400

Gnomad4 OTH AF: 0.0353

Alfa AF: 0.0405 Hom.: 16

Bravo AF: 0.0365

Asia WGS AF: 0.0430 AC: 149 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.20
DANN	Benign	0.74

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: rs35930240; hg19: chr19-49552068;