Variant 6-87088186-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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:

CGA (HGNC:):

CGA links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
CGA	NM_000735.4 linkuse as main transcript	c.15A>G	p.Arg5Arg	synonymous_variant	2/4	ENST00000627148.3	NP_000726.1	P01215Q6I9S8
CGA	NM_001252383.2 linkuse as main transcript	c.15A>G	p.Arg5Arg	synonymous_variant	2/5		NP_001239312.1	P01215A0A087WYZ4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CGA	ENST00000627148.3 linkuse as main transcript	c.15A>G	p.Arg5Arg	synonymous_variant	2/4	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

GnomAD3 exomes

AF:

0.0246

AC:

5579

AN:

226892

Hom.:

149

AF XY:

0.0236

AC XY:

2892

AN XY:

122640

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 SAS exome

AF:

0.0258

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

Gnomad4 AFR exome

AF:

0.117

Gnomad4 AMR exome

AF:

0.0121

Gnomad4 ASJ exome

AF:

0.00859

Gnomad4 EAS exome

AF:

0.0000770

Gnomad4 SAS exome

AF:

0.0266

Gnomad4 FIN exome

AF:

0.0242

Gnomad4 NFE exome

AF:

0.0202

Gnomad4 OTH exome

AF:

0.0234

GnomAD4 genome

AF:

0.0444

AC:

6659

AN:

149856

Hom.:

259

Cov.:

AF XY:

0.0434

AC XY:

3177

AN XY:

73208

show subpopulations

Gnomad4 AFR

AF:

0.110

Gnomad4 AMR

AF:

0.0176

Gnomad4 ASJ

AF:

0.00923

Gnomad4 EAS

AF:

0.000584

Gnomad4 SAS

AF:

0.0222

Gnomad4 FIN

AF:

0.0210

Gnomad4 NFE

AF:

0.0229

Gnomad4 OTH

AF:

0.0356

Alfa

AF:

0.0321

Hom.:

123

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

DANN

Benign

0.48

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over