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GeneBe

2-120349388-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_002193.4(INHBB):c.738C>T(p.Leu246=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00132 in 1,613,930 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00096 ( 1 hom., cov: 33)
Exomes 𝑓: 0.0014 ( 6 hom. )

Consequence

INHBB
NM_002193.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.760
Variant links:
Genes affected
INHBB (HGNC:6067): (inhibin subunit beta B) 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 the dimeric activin and inhibin protein complexes. These complexes activate and inhibit, respectively, follicle stimulating hormone secretion from the pituitary gland. Polymorphisms near this gene are associated with pre-eclampsia in female human patients. [provided by RefSeq, Aug 2016]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.53).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 2-120349388-C-T is Benign according to our data. Variant chr2-120349388-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2651315.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.76 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 146 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
INHBBNM_002193.4 linkuse as main transcriptc.738C>T p.Leu246= synonymous_variant 2/2 ENST00000295228.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
INHBBENST00000295228.4 linkuse as main transcriptc.738C>T p.Leu246= synonymous_variant 2/21 NM_002193.4 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000959
AC:
146
AN:
152208
Hom.:
1
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000217
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000262
Gnomad ASJ
AF:
0.00518
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000471
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00162
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00108
AC:
271
AN:
251190
Hom.:
1
AF XY:
0.00121
AC XY:
165
AN XY:
135820
show subpopulations
Gnomad AFR exome
AF:
0.000185
Gnomad AMR exome
AF:
0.000173
Gnomad ASJ exome
AF:
0.00635
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000653
Gnomad FIN exome
AF:
0.000370
Gnomad NFE exome
AF:
0.00159
Gnomad OTH exome
AF:
0.00130
GnomAD4 exome
AF:
0.00136
AC:
1981
AN:
1461604
Hom.:
6
Cov.:
31
AF XY:
0.00132
AC XY:
957
AN XY:
727112
show subpopulations
Gnomad4 AFR exome
AF:
0.000119
Gnomad4 AMR exome
AF:
0.000179
Gnomad4 ASJ exome
AF:
0.00597
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000464
Gnomad4 FIN exome
AF:
0.000527
Gnomad4 NFE exome
AF:
0.00154
Gnomad4 OTH exome
AF:
0.00114
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000958
AC:
146
AN:
152326
Hom.:
1
Cov.:
33
AF XY:
0.000873
AC XY:
65
AN XY:
74498
show subpopulations
Gnomad4 AFR
AF:
0.000216
Gnomad4 AMR
AF:
0.000261
Gnomad4 ASJ
AF:
0.00518
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000471
Gnomad4 NFE
AF:
0.00162
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.00172
Hom.:
0
Bravo
AF:
0.000990
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.00164
EpiControl
AF:
0.00130

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenJul 01, 2022INHBB: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.53
Cadd
Benign
5.5
Dann
Benign
0.93

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.

Other links and lift over

dbSNP: rs144317593; hg19: chr2-121106964; COSMIC: COSV54679477; API