Variant 12-57449928-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000309668.3(INHBC):c.965G>A(p.Arg322Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 1,589,440 control chromosomes in the GnomAD database, including 42,225 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.19 ( 3132 hom., cov: 32)

Exomes 𝑓: 0.22 ( 39093 hom. )

Consequence

INHBC
ENST00000309668.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.42

Variant links:

Genes affected

INHBC (HGNC:6068): (inhibin subunit beta C) This gene encodes a member of the TGF-beta (transforming growth factor-beta) superfamily of proteins. The encoded preproprotein is proteolytically processed to generate a subunit of homodimeric and heterodimeric activin complexes. The heterodimeric complex may function in the inhibition of activin A signaling. Transgenic mice overexpressing this gene exhibit defects in testis, liver and prostate. [provided by RefSeq, Aug 2016]

INHBC links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0042420924).

BP6

Variant 12-57449928-G-A is Benign according to our data. Variant chr12-57449928-G-A is described in ClinVar as [Benign]. Clinvar id is 1226227.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
INHBC	NM_005538.4 linkuse as main transcript	c.965G>A	p.Arg322Gln	missense_variant	2/2	ENST00000309668.3	NP_005529.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INHBC	ENST00000309668.3 linkuse as main transcript	c.965G>A	p.Arg322Gln	missense_variant	2/2	1	NM_005538.4	ENSP00000308716	P1

Frequencies

GnomAD3 genomes

AF:

0.186

AC:

28321

AN:

151996

Hom.:

3124

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0933

Gnomad AMI

AF:

0.304

Gnomad AMR

AF:

0.278

Gnomad ASJ

AF:

0.159

Gnomad EAS

AF:

0.0796

Gnomad SAS

AF:

0.0820

Gnomad FIN

AF:

0.230

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.232

Gnomad OTH

AF:

0.174

GnomAD3 exomes

AF:

0.216

AC:

50291

AN:

232398

Hom.:

7117

AF XY:

0.204

AC XY:

25534

AN XY:

125032

show subpopulations

Gnomad AFR exome

AF:

0.0907

Gnomad AMR exome

AF:

0.430

Gnomad ASJ exome

AF:

0.156

Gnomad EAS exome

AF:

0.0708

Gnomad SAS exome

AF:

0.0895

Gnomad FIN exome

AF:

0.226

Gnomad NFE exome

AF:

0.232

Gnomad OTH exome

AF:

0.205

GnomAD4 exome

AF:

0.222

AC:

319221

AN:

1437326

Hom.:

39093

Cov.:

AF XY:

0.216

AC XY:

153872

AN XY:

712212

show subpopulations

Gnomad4 AFR exome

AF:

0.0850

Gnomad4 AMR exome

AF:

0.409

Gnomad4 ASJ exome

AF:

0.152

Gnomad4 EAS exome

AF:

0.0808

Gnomad4 SAS exome

AF:

0.0888

Gnomad4 FIN exome

AF:

0.230

Gnomad4 NFE exome

AF:

0.238

Gnomad4 OTH exome

AF:

0.190

GnomAD4 genome

AF:

0.186

AC:

28342

AN:

152114

Hom.:

3132

Cov.:

AF XY:

0.183

AC XY:

13641

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.0933

Gnomad4 AMR

AF:

0.279

Gnomad4 ASJ

AF:

0.159

Gnomad4 EAS

AF:

0.0794

Gnomad4 SAS

AF:

0.0814

Gnomad4 FIN

AF:

0.230

Gnomad4 NFE

AF:

0.232

Gnomad4 OTH

AF:

0.172

Alfa

AF:

0.209

Hom.:

3758

Bravo

AF:

0.194

TwinsUK

AF:

0.243

AC:

901

ALSPAC

AF:

0.236

AC:

909

ESP6500AA

AF:

0.0956

AC:

421

ESP6500EA

AF:

0.227

AC:

1950

ExAC

AF:

0.209

AC:

25362

Asia WGS

AF:

0.105

AC:

366

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 18, 2019	This variant is associated with the following publications: (PMID: 30315176) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.73

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.52

LIST_S2

Benign

0.79

MetaRNN

Benign

0.0042

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.8

REVEL

Benign

0.12

Sift

Benign

0.065

Sift4G

Uncertain

0.057

Polyphen

0.28

Vest4

0.056

MPC

0.49

ClinPred

0.014

GERP RS

2.4

Varity_R

0.33

gMVP

0.82

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over