dbSNP rs6155: CGA:p.Arg5Arg (chr6-87088186-T-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_000735.4(CGA):c.15A>G(p.Arg5Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0242 in 1,585,232 control chromosomes in the GnomAD database, including 835 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 0.044 ( 259 hom., cov: 31)

Exomes 𝑓: 0.022 ( 576 hom. )

Consequence

CGA
NM_000735.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.278

Publications

6 publications found

Variant links:

Genes affected

CGA (HGNC:1885): (glycoprotein hormones, alpha polypeptide) The four human glycoprotein hormones chorionic gonadotropin (CG), luteinizing hormone (LH), follicle stimulating hormone (FSH), and thyroid stimulating hormone (TSH) are dimers consisting of alpha and beta subunits that are associated noncovalently. The alpha subunits of these hormones are identical, however, their beta chains are unique and confer biological specificity. The protein encoded by this gene is the alpha subunit and belongs to the glycoprotein hormones alpha chain family. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2011]

CGA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP7

Synonymous conserved (PhyloP=0.278 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CGA	NM_000735.4 link	c.15A>G	p.Arg5Arg	synonymous_variant	Exon 2 of 4	ENST00000627148.3	NP_000726.1	P01215Q6I9S8
CGA	NM_001252383.2 link	c.15A>G	p.Arg5Arg	synonymous_variant	Exon 2 of 5		NP_001239312.1	P01215A0A087WYZ4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CGA	ENST00000627148.3 link	c.15A>G	p.Arg5Arg	synonymous_variant	Exon 2 of 4	1	NM_000735.4	ENSP00000486024.1		P01215

Frequencies

GnomAD3 genomes

AF:

0.0444

AC:

6650

AN:

149758

Hom.:

259

Cov.:

show subpopulations

Gnomad AFR

AF:

0.110

Gnomad AMI

AF:

0.00440

Gnomad AMR

AF:

0.0176

Gnomad ASJ

AF:

0.00923

Gnomad EAS

AF:

0.000583

Gnomad SAS

AF:

0.0220

Gnomad FIN

AF:

0.0210

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0229

Gnomad OTH

AF:

0.0360

GnomAD2 exomes

AF:

0.0246

AC:

5579

AN:

226892

AF XY:

0.0236

show subpopulations

Gnomad AFR exome

AF:

0.113

Gnomad AMR exome

AF:

0.0113

Gnomad ASJ exome

AF:

0.00969

Gnomad EAS exome

AF:

0.0000604

Gnomad FIN exome

AF:

0.0246

Gnomad NFE exome

AF:

0.0223

Gnomad OTH exome

AF:

0.0164

GnomAD4 exome

AF:

0.0220

AC:

31645

AN:

1435376

Hom.:

576

Cov.:

AF XY:

0.0222

AC XY:

15831

AN XY:

713690

show subpopulations

African (AFR)

AF:

0.117

AC:

3757

AN:

32216

American (AMR)

AF:

0.0121

AC:

520

AN:

42876

Ashkenazi Jewish (ASJ)

AF:

0.00859

AC:

218

AN:

25370

East Asian (EAS)

AF:

0.0000770

AC:

AN:

38936

South Asian (SAS)

AF:

0.0266

AC:

2195

AN:

82410

European-Finnish (FIN)

AF:

0.0242

AC:

1270

AN:

52390

Middle Eastern (MID)

AF:

0.0293

AC:

166

AN:

5666

European-Non Finnish (NFE)

AF:

0.0202

AC:

22137

AN:

1096476

Other (OTH)

AF:

0.0234

AC:

1379

AN:

59036

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

1242

2485

3727

4970

6212

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

894

1788

2682

3576

4470

<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:

0.0444

AC:

6659

AN:

149856

Hom.:

259

Cov.:

AF XY:

0.0434

AC XY:

3177

AN XY:

73208

show subpopulations

African (AFR)

AF:

0.110

AC:

4396

AN:

39864

American (AMR)

AF:

0.0176

AC:

266

AN:

15108

Ashkenazi Jewish (ASJ)

AF:

0.00923

AC:

AN:

3466

East Asian (EAS)

AF:

0.000584

AC:

AN:

5134

South Asian (SAS)

AF:

0.0222

AC:

106

AN:

4766

European-Finnish (FIN)

AF:

0.0210

AC:

218

AN:

10378

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0229

AC:

1557

AN:

67860

Other (OTH)

AF:

0.0356

AC:

AN:

2076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

261

522

782

1043

1304

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

136

204

272

340

<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:

0.0323

Hom.:

360

Bravo

AF:

0.0474

Asia WGS

AF:

0.0200

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

2.5

(source)

DANN

Benign

0.48

PhyloP100

0.28

Mutation Taster

=99/1

polymorphism (auto)

(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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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