Genetic Variant CGB5:c.15+171C>T (chr19-49044395-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_033043.2(CGB5):c.15+171C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00116 in 980,706 control chromosomes in the GnomAD database, including 6 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 0.0021 ( 0 hom., cov: 27)

Exomes 𝑓: 0.00099 ( 6 hom. )

Consequence

CGB5
NM_033043.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.05

Publications

1 publications found

Variant links:

Genes affected

CGB5 (HGNC:16452): (chorionic gonadotropin subunit beta 5) This gene is a member of the glycoprotein hormone beta chain family and encodes the beta 5 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]

CGB5 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CGB5	NM_033043.2 link	c.15+171C>T		intron_variant	Intron 1 of 2	ENST00000301408.7	NP_149032.1	P0DN86-1A0A0F7RQP8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CGB5	ENST00000301408.7 link	c.15+171C>T		intron_variant	Intron 1 of 2	1	NM_033043.2	ENSP00000301408.5		P0DN86-1

Frequencies

GnomAD3 genomes

AF:

0.00213

AC:

315

AN:

147950

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00409

Gnomad AMI

AF:

0.00221

Gnomad AMR

AF:

0.000793

Gnomad ASJ

AF:

0.00231

Gnomad EAS

AF:

0.000388

Gnomad SAS

AF:

0.000627

Gnomad FIN

AF:

0.000472

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00177

Gnomad OTH

AF:

0.00339

GnomAD4 exome

AF:

0.000991

AC:

825

AN:

832648

Hom.:

Cov.:

AF XY:

0.000988

AC XY:

380

AN XY:

384514

show subpopulations

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

African (AFR)

AF:

0.000709

AC:

AN:

15504

American (AMR)

AF:

0.00

AC:

AN:

982

Ashkenazi Jewish (ASJ)

AF:

0.00233

AC:

AN:

5152

East Asian (EAS)

AF:

0.00

AC:

AN:

3630

South Asian (SAS)

AF:

0.000669

AC:

AN:

16454

European-Finnish (FIN)

AF:

0.00362

AC:

AN:

276

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1620

European-Non Finnish (NFE)

AF:

0.000999

AC:

761

AN:

761746

Other (OTH)

AF:

0.00106

AC:

AN:

27284

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.387

Heterozygous variant carriers

107

142

178

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

160

200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00213

AC:

316

AN:

148058

Hom.:

Cov.:

AF XY:

0.00206

AC XY:

149

AN XY:

72372

show subpopulations

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

African (AFR)

AF:

0.00408

AC:

154

AN:

37756

American (AMR)

AF:

0.000792

AC:

AN:

15144

Ashkenazi Jewish (ASJ)

AF:

0.00231

AC:

AN:

3468

East Asian (EAS)

AF:

0.000389

AC:

AN:

5148

South Asian (SAS)

AF:

0.000627

AC:

AN:

4784

European-Finnish (FIN)

AF:

0.000472

AC:

AN:

10594

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00178

AC:

121

AN:

67876

Other (OTH)

AF:

0.00335

AC:

AN:

2088

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.357

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00275

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.064

(source)

DANN

Benign

0.30

PhyloP100

-2.0

Mutation Taster

=100/0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over