rs34315612

Variant names:

• chr19-49033309-T-C
• rs34315612
• ENST00000591656.1:c.-28+3217A>G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The ENST00000604577.1(ENSG00000267335):​c.9+3394A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0051 in 1,606,264 control chromosomes in the GnomAD database, including 55 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 0.0038 (1 hom., cov: 30)
  • Exomes 𝑓: 0.0052 (54 hom.)
• Consequence: ENSG00000267335 ENST00000604577.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.805

Genes affected

ENSG00000267335 (HGNC:):

CGB2 (HGNC:16722): (chorionic gonadotropin subunit beta 2) The beta subunit of chorionic gonadotropin (CGB) is encoded by six highly homologous and structurally similar genes that are arranged in tandem and inverted pairs on chromosome 19q13.3, and contiguous with the luteinizing hormone beta (LHB) subunit gene. The CGB genes are primarily distinguished by differences in the 5' untranscribed region. This gene was originally thought to be one of the two pseudogenes (CGB1 and CGB2) of CGB subunit, however, detection of CGB1 and CGB2 transcripts in vivo, and their presence on the polysomes, suggested that these transcripts are translated. To date, a protein product corresponding to CGB2 has not been isolated. The deduced sequence of the hypothetical protein of 132 aa does not share any similarity with that of functional CGB subunits (PMID:8954017). However, a 163 aa protein, translated from a different frame, is about the same size, and shares 98% identity with other CGB subunits. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BS2: High Homozygotes in GnomAdExome4 at 54 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CGB2	NM_033378.2	c.*88T>C		downstream_gene_variant		ENST00000359342.7	NP_203696.2
CGB2	NM_001319065.2	c.*88T>C		downstream_gene_variant			NP_001305994.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000267335	ENST00000591656.1	c.-28+3217A>G		intron_variant	Intron 1 of 2	2		ENSP00000466140.1
ENSG00000267335	ENST00000604577.1	c.9+3394A>G		intron_variant	Intron 1 of 2	1		ENSP00000474022.1
CGB2	ENST00000359342.7	c.*88T>C		downstream_gene_variant		1	NM_033378.2	ENSP00000352295.6
CGB2	ENST00000474913.1	c.*155T>C		downstream_gene_variant		1		ENSP00000471177.1

Frequencies

GnomAD3 genomes AF: 0.00380 AC: 577 AN: 151892 Hom.: 1 Cov.: 30

Gnomad AFR AF: 0.000970

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00203

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00415

Gnomad FIN AF: 0.00905

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00547

Gnomad OTH AF: 0.00144

GnomAD4 exome AF: 0.00524 AC: 7620 AN: 1454254 Hom.: 54 AF XY: 0.00527 AC XY: 3809 AN XY: 723004

Gnomad4 AFR exome AF: 0.000723

Gnomad4 AMR exome AF: 0.00341

Gnomad4 ASJ exome AF: 0.00237

Gnomad4 EAS exome AF: 0.0000757

Gnomad4 SAS exome AF: 0.00689

Gnomad4 FIN exome AF: 0.00779

Gnomad4 NFE exome AF: 0.00546

Gnomad4 OTH exome AF: 0.00522

GnomAD4 genome AF: 0.00379 AC: 576 AN: 152010 Hom.: 1 Cov.: 30 AF XY: 0.00390 AC XY: 290 AN XY: 74296

Gnomad4 AFR AF: 0.000967

Gnomad4 AMR AF: 0.00203

Gnomad4 ASJ AF: 0.00346

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00395

Gnomad4 FIN AF: 0.00905

Gnomad4 NFE AF: 0.00547

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00376 Hom.: 0

Bravo AF: 0.00321

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	16
DANN	Benign	0.28

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: rs34315612; hg19: chr19-49536566;