NM_000737.5:c.-228G>A

Variant names:

• chr19-49024199-C-T
• rs710899
• NM_000737.5:c.-228G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000737.5(CGB3):​c.-228G>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 0.0000794 in 151,074 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000079 (0 hom., cov: 25)
  • Exomes 𝑓: 0.000024 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CGB3 NM_000737.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0130
• Publications: 3 publications found

Genes affected

CGB3 (HGNC:1886): (chorionic gonadotropin subunit beta 3) This gene is a member of the glycoprotein hormone beta chain family and encodes the beta 3 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]

ENSG00000267335 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CGB3	NM_000737.5	c.-228G>A		5_prime_UTR_variant	Exon 1 of 3	ENST00000357383.4	NP_000728.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CGB3	ENST00000357383.4	c.-228G>A		5_prime_UTR_variant	Exon 1 of 3	1	NM_000737.5	ENSP00000349954.2
ENSG00000267335	ENST00000591656.1	c.-27-596G>A		intron_variant	Intron 1 of 2	2		ENSP00000466140.1
ENSG00000267335	ENST00000604577.1	c.10-596G>A		intron_variant	Intron 1 of 2	1		ENSP00000474022.1

Frequencies

GnomAD3 genomes AF: 0.0000795 AC: 12 AN: 150956 Hom.: 0 Cov.: 25

Gnomad AFR AF: 0.000246

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000480

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000240 AC: 31 AN: 1293316 Hom.: 0 Cov.: 26 AF XY: 0.0000238 AC XY: 15 AN XY: 630390

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000553 AC: 15 AN: 27102

American (AMR) AF: 0.0000435 AC: 1 AN: 22974

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19194

East Asian (EAS) AF: 0.0000285 AC: 1 AN: 35030

South Asian (SAS) AF: 0.0000601 AC: 4 AN: 66604

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36438

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3578

European-Non Finnish (NFE) AF: 0.00000972 AC: 10 AN: 1028980

Other (OTH) AF: 0.00 AC: 0 AN: 53416

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000794 AC: 12 AN: 151074 Hom.: 0 Cov.: 25 AF XY: 0.0000813 AC XY: 6 AN XY: 73810

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000245 AC: 10 AN: 40754

American (AMR) AF: 0.00 AC: 0 AN: 15200

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5122

South Asian (SAS) AF: 0.000209 AC: 1 AN: 4796

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10580

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67850

Other (OTH) AF: 0.000475 AC: 1 AN: 2106

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00000000000000521805), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0000843 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.5
DANN	Benign	0.90
PhyloP100		0.013
PromoterAI		-0.015	Neutral

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

Other links and lift over

dbSNP: rs710899; hg19: chr19-49527456;