rs1001328649

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005538.4(INHBC):ā€‹c.340C>Gā€‹(p.Leu114Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,906 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

INHBC
NM_005538.4 missense

Scores

2
7
10

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.98
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
INHBCNM_005538.4 linkc.340C>G p.Leu114Val missense_variant Exon 2 of 2 ENST00000309668.3 NP_005529.1 P55103

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
INHBCENST00000309668.3 linkc.340C>G p.Leu114Val missense_variant Exon 2 of 2 1 NM_005538.4 ENSP00000308716.2 P55103

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152224
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461682
Hom.:
0
Cov.:
35
AF XY:
0.00000138
AC XY:
1
AN XY:
727150
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152224
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74376
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000282
Hom.:
0
Bravo
AF:
0.00000378
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Uncertain
0.034
T
BayesDel_noAF
Benign
-0.19
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.28
T
Eigen
Uncertain
0.50
Eigen_PC
Uncertain
0.48
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Benign
0.73
T
M_CAP
Benign
0.022
T
MetaRNN
Uncertain
0.49
T
MetaSVM
Benign
-0.60
T
MutationAssessor
Pathogenic
3.1
M
PrimateAI
Benign
0.46
T
PROVEAN
Benign
-1.8
N
REVEL
Benign
0.25
Sift
Uncertain
0.0080
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.34
MutPred
0.48
Gain of catalytic residue at F118 (P = 0.0058);
MVP
0.88
MPC
0.71
ClinPred
0.98
D
GERP RS
4.8
Varity_R
0.30
gMVP
0.57

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

LitVar

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

Other links and lift over

dbSNP: rs1001328649; hg19: chr12-57843086; API