chr19-49054580-G-A

Variant names:

• chr19-49054580-G-A
• rs1449735785
• NM_001385261.1:c.209C>T

Variant summary

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

The NM_001385261.1(CGB7):​c.209C>T​(p.Pro70Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000038 (0 hom., cov: 18)
  • Exomes 𝑓: 0.00011 (3 hom.)
  • Failed GnomAD Quality Control
• Consequence: CGB7 NM_001385261.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.575
• Publications: 0 publications found

Genes affected

CGB7 (HGNC:16451): (chorionic gonadotropin subunit beta 7) This gene is a member of the glycoprotein hormone beta chain family and encodes the beta 7 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

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.056654453).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CGB7	NM_001385261.1	c.209C>T	p.Pro70Leu	missense_variant	Exon 5 of 5	ENST00000684222.1	NP_001372190.1
CGB7	NM_033142.2	c.209C>T	p.Pro70Leu	missense_variant	Exon 5 of 5		NP_149133.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CGB7	ENST00000684222.1	c.209C>T	p.Pro70Leu	missense_variant	Exon 5 of 5		NM_001385261.1	ENSP00000507822.1
CGB7	ENST00000596965.5	c.209C>T	p.Pro70Leu	missense_variant	Exon 5 of 5	2		ENSP00000469076.1
CGB7	ENST00000597853.5	c.209C>T	p.Pro70Leu	missense_variant	Exon 5 of 5	2		ENSP00000470813.1

Frequencies

GnomAD3 genomes AF: 0.0000380 AC: 5 AN: 131440 Hom.: 0 Cov.: 18

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00136

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000293 AC: 17 AN: 57980 AF XY: 0.000376

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000249

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000113 AC: 122 AN: 1079638 Hom.: 3 Cov.: 17 AF XY: 0.000168 AC XY: 90 AN XY: 536988

African (AFR) AF: 0.00 AC: 0 AN: 27712

American (AMR) AF: 0.00 AC: 0 AN: 32410

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20624

East Asian (EAS) AF: 0.000175 AC: 6 AN: 34230

South Asian (SAS) AF: 0.00162 AC: 109 AN: 67112

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34836

Middle Eastern (MID) AF: 0.000294 AC: 1 AN: 3404

European-Non Finnish (NFE) AF: 0.00000246 AC: 2 AN: 812068

Other (OTH) AF: 0.0000847 AC: 4 AN: 47242

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000380 AC: 5 AN: 131542 Hom.: 0 Cov.: 18 AF XY: 0.0000794 AC XY: 5 AN XY: 62980

African (AFR) AF: 0.00 AC: 0 AN: 36466

American (AMR) AF: 0.00 AC: 0 AN: 13212

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3192

East Asian (EAS) AF: 0.00 AC: 0 AN: 4446

South Asian (SAS) AF: 0.00136 AC: 5 AN: 3678

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8162

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 280

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 59510

Other (OTH) AF: 0.00 AC: 0 AN: 1740

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 29, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.209C>T (p.P70L) alteration is located in exon 3 (coding exon 3) of the CGB7 gene. This alteration results from a C to T substitution at nucleotide position 209, causing the proline (P) at amino acid position 70 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	15
DANN	Benign	0.81
DEOGEN2	Uncertain	0.57	D;D;D
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.79	T;.;.
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.057	T;T;T
MetaSVM	Benign	-0.41	T
PhyloP100		0.57
PROVEAN	Uncertain	-2.7	D;.;.
REVEL	Benign	0.17
Sift	Benign	0.085	T;.;.
Sift4G	Uncertain	0.040	D;D;D
Vest4		0.26
MVP		0.46
MPC		1.1
ClinPred		0.031	T
GERP RS		0.63
Varity_R		0.061
gMVP		0.17
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1449735785; hg19: chr19-49557837;