2-120346327-T-G

Variant names:

• chr2-120346327-T-G
• rs11900747
• NM_002193.4:c.139T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000295228.4(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. 15/21 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 ENST00000295228.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0820
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000295228.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INHBB	NM_002193.4	MANE Select	c.139T>G	p.Ser47Ala	missense	Exon 1 of 2	NP_002184.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INHBB	ENST00000295228.4	TSL:1 MANE Select	c.139T>G	p.Ser47Ala	missense	Exon 1 of 2	ENSP00000295228.3

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

GnomAD2 exomes AF: 0.0736 AC: 1265 AN: 17196 AF XY: 0.0814

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 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

African (AFR) AF: 0.441 AC: 10580 AN: 23970

American (AMR) AF: 0.0655 AC: 876 AN: 13372

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 2768 AN: 17826

East Asian (EAS) AF: 0.218 AC: 5979 AN: 27444

South Asian (SAS) AF: 0.281 AC: 15638 AN: 55680

European-Finnish (FIN) AF: 0.0494 AC: 1663 AN: 33668

Middle Eastern (MID) AF: 0.172 AC: 604 AN: 3506

European-Non Finnish (NFE) AF: 0.0670 AC: 67544 AN: 1008416

Other (OTH) AF: 0.120 AC: 6090 AN: 50642

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

African (AFR) AF: 0.420 AC: 17322 AN: 41284

American (AMR) AF: 0.104 AC: 1589 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 554 AN: 3416

East Asian (EAS) AF: 0.162 AC: 813 AN: 5004

South Asian (SAS) AF: 0.299 AC: 1433 AN: 4796

European-Finnish (FIN) AF: 0.0541 AC: 564 AN: 10426

Middle Eastern (MID) AF: 0.162 AC: 47 AN: 290

European-Non Finnish (NFE) AF: 0.0727 AC: 4877 AN: 67106

Other (OTH) AF: 0.160 AC: 333 AN: 2078

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 v4.9

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
PhyloP100		-0.082
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
PromoterAI		-0.044	Neutral
Varity_R		0.071
gMVP		0.079
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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