rs34315612

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The ENST00000591656.1(ENSG00000267335):​c.-28+3217A>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 ENST00000591656.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.805
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -8 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000591656.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CGB2	NM_033378.2	MANE Select	c.*88T>C		downstream_gene	N/A	NP_203696.2
	CGB2	NM_001319065.2		c.*88T>C		downstream_gene	N/A	NP_001305994.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000267335	ENST00000591656.1	TSL:2	c.-28+3217A>G		intron	N/A	ENSP00000466140.1
	ENSG00000267335	ENST00000604577.1	TSL:1	c.9+3394A>G		intron	N/A	ENSP00000474022.1
	CGB2	ENST00000359342.7	TSL:1 MANE Select	c.*88T>C		downstream_gene	N/A	ENSP00000352295.6

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

African (AFR) AF: 0.000723 AC: 24 AN: 33182

American (AMR) AF: 0.00341 AC: 151 AN: 44256

Ashkenazi Jewish (ASJ) AF: 0.00237 AC: 61 AN: 25708

East Asian (EAS) AF: 0.0000757 AC: 3 AN: 39654

South Asian (SAS) AF: 0.00689 AC: 586 AN: 85062

European-Finnish (FIN) AF: 0.00779 AC: 414 AN: 53142

Middle Eastern (MID) AF: 0.00215 AC: 9 AN: 4178

European-Non Finnish (NFE) AF: 0.00546 AC: 6059 AN: 1109086

Other (OTH) AF: 0.00522 AC: 313 AN: 59986

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

African (AFR) AF: 0.000967 AC: 40 AN: 41350

American (AMR) AF: 0.00203 AC: 31 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00346 AC: 12 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5168

South Asian (SAS) AF: 0.00395 AC: 19 AN: 4812

European-Finnish (FIN) AF: 0.00905 AC: 96 AN: 10602

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00547 AC: 372 AN: 68004

Other (OTH) AF: 0.00142 AC: 3 AN: 2108

Alfa AF: 0.00376 Hom.: 0

Bravo AF: 0.00321

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	16
DANN	Benign	0.28
PhyloP100		0.81

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

Other links and lift over

dbSNP: rs34315612; hg19: chr19-49536566;