chr19-49054445-C-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001385261.1(CGB7):c.344G>A(p.Arg115His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000107 in 1,594,274 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000041 ( 0 hom., cov: 21)

Exomes 𝑓: 0.0000076 ( 0 hom. )

Consequence

CGB7
NM_001385261.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.61

Publications

1 publications found

Variant links:

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]

CGB7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14547324).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CGB7	NM_001385261.1 link	c.344G>A	p.Arg115His	missense_variant	Exon 5 of 5	ENST00000684222.1	NP_001372190.1
CGB7	NM_033142.2 link	c.344G>A	p.Arg115His	missense_variant	Exon 5 of 5		NP_149133.1	P0DN87A0A0F7RQF0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CGB7	ENST00000684222.1 link	c.344G>A	p.Arg115His	missense_variant	Exon 5 of 5		NM_001385261.1	ENSP00000507822.1	P0DN87
CGB7	ENST00000596965.5 link	c.344G>A	p.Arg115His	missense_variant	Exon 5 of 5	2		ENSP00000469076.1	P0DN87
CGB7	ENST00000597853.5 link	c.344G>A	p.Arg115His	missense_variant	Exon 5 of 5	2		ENSP00000470813.1	P0DN87

Frequencies

GnomAD3 genomes

AF:

0.0000412

AC:

AN:

145596

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000100

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000304

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000199

AC:

AN:

100754

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.000128

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000255

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000759

AC:

AN:

1448564

Hom.:

Cov.:

AF XY:

0.00000694

AC XY:

AN XY:

720128

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33276

American (AMR)

AF:

0.00

AC:

AN:

43748

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25704

East Asian (EAS)

AF:

0.00

AC:

AN:

39528

South Asian (SAS)

AF:

0.0000235

AC:

AN:

85084

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52944

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4104

European-Non Finnish (NFE)

AF:

0.00000724

AC:

AN:

1104438

Other (OTH)

AF:

0.0000167

AC:

AN:

59738

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.416

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000412

AC:

AN:

145710

Hom.:

Cov.:

AF XY:

0.0000284

AC XY:

AN XY:

70530

show subpopulations

African (AFR)

AF:

0.000100

AC:

AN:

39942

American (AMR)

AF:

0.00

AC:

AN:

14398

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3414

East Asian (EAS)

AF:

0.00

AC:

AN:

4884

South Asian (SAS)

AF:

0.00

AC:

AN:

4298

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9812

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000304

AC:

AN:

65808

Other (OTH)

AF:

0.00

AC:

AN:

1964

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.558

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.0000310

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 04, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.344G>A (p.R115H) alteration is located in exon 3 (coding exon 3) of the CGB7 gene. This alteration results from a G to A substitution at nucleotide position 344, causing the arginine (R) at amino acid position 115 to be replaced by a histidine (H). 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

0.18

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.53

D;D;D

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.45

FATHMM_MKL

Benign

0.22

LIST_S2

Pathogenic

0.98

D;.;.

M_CAP

Benign

0.028

MetaRNN

Benign

0.15

T;T;T

MetaSVM

Benign

-0.85

PhyloP100

1.6

PROVEAN

Benign

-1.6

N;.;.

REVEL

Benign

0.088

Sift

Uncertain

0.0070

D;.;.

Sift4G

Uncertain

0.031

D;D;D

Vest4

0.24

MVP

0.28

MPC

2.4

ClinPred

0.88

GERP RS

0.75

Varity_R

0.074

gMVP

0.083

Mutation Taster

=96/4

polymorphism

(source)

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

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chr19-49054445-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over