19-49035873-C-G

Variant names:

• chr19-49035873-C-G
• rs574589925
• NM_033377.2:c.205G>C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_033377.2(CGB1):​c.205G>C​(p.Ala69Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0039 (1 hom., cov: 25)
  • Exomes 𝑓: 0.0060 (23 hom.)
  • Failed GnomAD Quality Control
• Consequence: CGB1 NM_033377.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.281

Genes affected

CGB1 (HGNC:16721): (chorionic gonadotropin subunit beta 1) 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 CGB1 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 155 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]

ENSG00000267335 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.006509602).
• BP6: Variant 19-49035873-C-G is Benign according to our data. Variant chr19-49035873-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2650232.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CGB1	NM_033377.2	c.205G>C	p.Ala69Pro	missense_variant	Exon 3 of 3	ENST00000301407.8	NP_203695.2
CGB1	NM_001382421.1	c.169G>C	p.Ala57Pro	missense_variant	Exon 3 of 3		NP_001369350.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CGB1	ENST00000301407.8	c.205G>C	p.Ala69Pro	missense_variant	Exon 3 of 3	1	NM_033377.2	ENSP00000301407.6
ENSG00000267335	ENST00000591656.1	c.-28+653G>C		intron_variant	Intron 1 of 2	2		ENSP00000466140.1
ENSG00000267335	ENST00000604577.1	c.9+830G>C		intron_variant	Intron 1 of 2	1		ENSP00000474022.1
CGB1	ENST00000601167.1	c.169G>C	p.Ala57Pro	missense_variant	Exon 3 of 3	5		ENSP00000472896.2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 576 AN: 146314 Hom.: 1 Cov.: 25 FAILED QC

Gnomad AFR AF: 0.000957

Gnomad AMI AF: 0.00225

Gnomad AMR AF: 0.00596

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00178

Gnomad FIN AF: 0.00119

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00631

Gnomad OTH AF: 0.00408

GnomAD3 exomes AF: 0.00420 AC: 449 AN: 106988 Hom.: 7 AF XY: 0.00432 AC XY: 244 AN XY: 56546

Gnomad AFR exome AF: 0.000469

Gnomad AMR exome AF: 0.00435

Gnomad ASJ exome AF: 0.000207

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00170

Gnomad FIN exome AF: 0.00210

Gnomad NFE exome AF: 0.00720

Gnomad OTH exome AF: 0.00783

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00596 AC: 7717 AN: 1295774 Hom.: 23 Cov.: 26 AF XY: 0.00587 AC XY: 3754 AN XY: 640016

Gnomad4 AFR exome AF: 0.000728

Gnomad4 AMR exome AF: 0.00466

Gnomad4 ASJ exome AF: 0.000439

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00160

Gnomad4 FIN exome AF: 0.00131

Gnomad4 NFE exome AF: 0.00706

Gnomad4 OTH exome AF: 0.00496

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00393 AC: 576 AN: 146428 Hom.: 1 Cov.: 25 AF XY: 0.00386 AC XY: 275 AN XY: 71232

Gnomad4 AFR AF: 0.000954

Gnomad4 AMR AF: 0.00595

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00178

Gnomad4 FIN AF: 0.00119

Gnomad4 NFE AF: 0.00631

Gnomad4 OTH AF: 0.00404

Alfa AF: 0.00356 Hom.: 1

Bravo AF: 0.00413

ExAC AF: 0.00173 AC: 153

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

CGB1: BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	9.3
DANN	Benign	0.39
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.00058	N
LIST_S2	Benign	0.47	T;T
MetaRNN	Benign	0.0065	T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	1.4	N;.
REVEL	Benign	0.063
Sift	Benign	1.0	T;.
Sift4G	Benign	0.91	T;.
Polyphen		0.0010	B;.
Vest4		0.17
MVP		0.040
MPC		1.5
ClinPred		0.0027	T
GERP RS		-0.62
gMVP		0.27

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: rs574589925; hg19: chr19-49539130;