Variant 6-87085839-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_000735.4(CGA):c.274-6C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000686 in 1,591,530 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0038 ( 4 hom., cov: 32)

Exomes 𝑓: 0.00036 ( 2 hom. )

Consequence

CGA
NM_000735.4 splice_region, intron

Scores

Splicing: ADA: 0.00003147

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.118

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 6-87085839-G-A is Benign according to our data. Variant chr6-87085839-G-A is described in ClinVar as [Benign]. Clinvar id is 714315.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CGA	NM_000735.4 linkuse as main transcript	c.274-6C>T		splice_region_variant, intron_variant		ENST00000627148.3	NP_000726.1	P01215Q6I9S8
CGA	NM_001252383.2 linkuse as main transcript	c.367-6C>T		splice_region_variant, intron_variant			NP_001239312.1	P01215A0A087WYZ4

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CGA	ENST00000627148.3 linkuse as main transcript	c.274-6C>T	splice_region_variant, intron_variant		1	NM_000735.4	ENSP00000486024.1	P01215
CGA	ENST00000630630.2 linkuse as main transcript	c.*378C>T	3_prime_UTR_variant	3/3	2		ENSP00000487300.1	A0A0D9SGA7
CGA	ENST00000610310.3 linkuse as main transcript	c.367-6C>T	splice_region_variant, intron_variant		3		ENSP00000482232.1	A0A087WYZ4
CGA	ENST00000369582.6 linkuse as main transcript	c.274-6C>T	splice_region_variant, intron_variant		5		ENSP00000358595.3	A0A0R4J2F0

Frequencies

GnomAD3 genomes

AF:

0.00378

AC:

574

AN:

151872

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0134

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

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:

0.0000589

Gnomad OTH

AF:

0.00240

GnomAD3 exomes

AF:

0.000947

AC:

233

AN:

245938

Hom.:

AF XY:

0.000632

AC XY:

AN XY:

132960

show subpopulations

Gnomad AFR exome

AF:

0.0128

Gnomad AMR exome

AF:

0.000642

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000272

Gnomad OTH exome

AF:

0.000497

GnomAD4 exome

AF:

0.000359

AC:

517

AN:

1439540

Hom.:

Cov.:

AF XY:

0.000298

AC XY:

214

AN XY:

717402

show subpopulations

Gnomad4 AFR exome

AF:

0.0122

Gnomad4 AMR exome

AF:

0.000764

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000820

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000549

Gnomad4 OTH exome

AF:

0.00111

GnomAD4 genome

AF:

0.00378

AC:

575

AN:

151990

Hom.:

Cov.:

AF XY:

0.00350

AC XY:

260

AN XY:

74282

show subpopulations

Gnomad4 AFR

AF:

0.0134

Gnomad4 AMR

AF:

0.000720

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000589

Gnomad4 OTH

AF:

0.00238

Alfa

AF:

0.00169

Hom.:

Bravo

AF:

0.00456

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 30, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.1

DANN

Benign

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000031

dbscSNV1_RF

Benign

0.0

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over