Genetic Variant CGB7:p.Leu112Phe (chr19-49054455-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

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

The NM_001385261.1(CGB7):c.334C>T(p.Leu112Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000076 ( 0 hom., cov: 20)

Exomes 𝑓: 0.00018 ( 2 hom. )

Failed GnomAD Quality Control

Consequence

CGB7
NM_001385261.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.42

Publications

0 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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.035449624).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CGB7	NM_001385261.1 link	c.334C>T	p.Leu112Phe	missense_variant	Exon 5 of 5	ENST00000684222.1	NP_001372190.1
CGB7	NM_033142.2 link	c.334C>T	p.Leu112Phe	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.334C>T	p.Leu112Phe	missense_variant	Exon 5 of 5		NM_001385261.1	ENSP00000507822.1	P0DN87
CGB7	ENST00000596965.5 link	c.334C>T	p.Leu112Phe	missense_variant	Exon 5 of 5	2		ENSP00000469076.1	P0DN87
CGB7	ENST00000597853.5 link	c.334C>T	p.Leu112Phe	missense_variant	Exon 5 of 5	2		ENSP00000470813.1	P0DN87

Frequencies

GnomAD3 genomes

AF:

0.0000759

AC:

AN:

144954

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000177

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000938

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000307

AC:

AN:

94548

AF XY:

0.000348

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.0000276

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000176

AC:

255

AN:

1447154

Hom.:

Cov.:

AF XY:

0.000250

AC XY:

180

AN XY:

719414

show subpopulations

African (AFR)

AF:

0.000210

AC:

AN:

33272

American (AMR)

AF:

0.00

AC:

AN:

43936

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25734

East Asian (EAS)

AF:

0.00

AC:

AN:

39512

South Asian (SAS)

AF:

0.00275

AC:

234

AN:

85150

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52880

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4112

European-Non Finnish (NFE)

AF:

0.00000363

AC:

AN:

1102860

Other (OTH)

AF:

0.000168

AC:

AN:

59698

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000758

AC:

AN:

145072

Hom.:

Cov.:

AF XY:

0.0000997

AC XY:

AN XY:

70234

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000176

AC:

AN:

39780

American (AMR)

AF:

0.00

AC:

AN:

14308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3420

East Asian (EAS)

AF:

0.00

AC:

AN:

4876

South Asian (SAS)

AF:

0.000939

AC:

AN:

4260

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9776

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

65528

Other (OTH)

AF:

0.00

AC:

AN:

1942

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.008343), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.000149

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 06, 2021

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.334C>T (p.L112F) 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 334, causing the leucine (L) at amino acid position 112 to be replaced by a phenylalanine (F). 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

0.14

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.28

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Uncertain

0.64

D;D;D

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.52

FATHMM_MKL

Uncertain

0.80

LIST_S2

Uncertain

0.88

D;.;.

M_CAP

Benign

0.071

MetaRNN

Benign

0.035

T;T;T

MetaSVM

Uncertain

-0.099

PhyloP100

1.4

PROVEAN

Uncertain

-2.6

D;.;.

REVEL

Uncertain

0.34

Sift

Benign

0.45

T;.;.

Sift4G

Benign

0.13

T;T;T

Vest4

0.16

MVP

0.62

MPC

1.9

ClinPred

0.094

GERP RS

0.67

Varity_R

0.13

gMVP

0.034

Mutation Taster

=95/5

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

19-49054455-G-A

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