2-120346327-T-G

Position:

• chr2-120346327-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002193.4(INHBB):​c.139T>G​(p.Ser47Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 1,385,044 control chromosomes in the GnomAD database, including 13,016 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.18 (4335 hom., cov: 32)
  • Exomes 𝑓: 0.091 (8681 hom.)
• Consequence: INHBB NM_002193.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0820

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=9.382069E-4).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
INHBB	NM_002193.4	c.139T>G	p.Ser47Ala	missense_variant	1/2	ENST00000295228.4	NP_002184.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INHBB	ENST00000295228.4	c.139T>G	p.Ser47Ala	missense_variant	1/2	1	NM_002193.4	ENSP00000295228	P1

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27518 AN: 150426 Hom.: 4322 Cov.: 32

Gnomad AFR AF: 0.419

Gnomad AMI AF: 0.0330

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.0541

Gnomad MID AF: 0.163

Gnomad NFE AF: 0.0727

Gnomad OTH AF: 0.157

GnomAD3 exomes AF: 0.0736 AC: 1265 AN: 17196 Hom.: 95 AF XY: 0.0814 AC XY: 781 AN XY: 9594

Gnomad AFR exome AF: 0.338

Gnomad AMR exome AF: 0.0361

Gnomad ASJ exome AF: 0.104

Gnomad EAS exome AF: 0.119

Gnomad SAS exome AF: 0.188

Gnomad FIN exome AF: 0.0356

Gnomad NFE exome AF: 0.0503

Gnomad OTH exome AF: 0.0959

GnomAD4 exome AF: 0.0905 AC: 111742 AN: 1234524 Hom.: 8681 Cov.: 33 AF XY: 0.0944 AC XY: 56597 AN XY: 599822

Gnomad4 AFR exome AF: 0.441

Gnomad4 AMR exome AF: 0.0655

Gnomad4 ASJ exome AF: 0.155

Gnomad4 EAS exome AF: 0.218

Gnomad4 SAS exome AF: 0.281

Gnomad4 FIN exome AF: 0.0494

Gnomad4 NFE exome AF: 0.0670

Gnomad4 OTH exome AF: 0.120

GnomAD4 genome AF: 0.183 AC: 27562 AN: 150520 Hom.: 4335 Cov.: 32 AF XY: 0.184 AC XY: 13510 AN XY: 73452

Gnomad4 AFR AF: 0.420

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.162

Gnomad4 EAS AF: 0.162

Gnomad4 SAS AF: 0.299

Gnomad4 FIN AF: 0.0541

Gnomad4 NFE AF: 0.0727

Gnomad4 OTH AF: 0.160

Alfa AF: 0.125 Hom.: 287

Bravo AF: 0.190

ExAC AF: 0.0464 AC: 2674

Asia WGS AF: 0.275 AC: 940 AN: 3428

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	15
DANN	Benign	0.38
DEOGEN2	Benign	0.26	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.067	N
LIST_S2	Benign	0.091	T
MetaRNN	Benign	0.00094	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	1.0	P
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	0.24	N
REVEL	Benign	0.22
Sift	Benign	0.64	T
Sift4G	Benign	0.96	T
Polyphen		0.0	B
Vest4		0.016
MPC		1.4
ClinPred		0.00018	T
GERP RS		2.5
Varity_R		0.071
gMVP		0.079

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

Other links and lift over

dbSNP: rs11900747; hg19: chr2-121103903; COSMIC: COSV54677472;