2-120349370-G-A

Position:

• chr2-120349370-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_002193.4(INHBB):​c.720G>A​(p.Glu240=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000226 in 1,614,006 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00018 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00023 (2 hom.)
• Consequence: INHBB NM_002193.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.431

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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP7: Synonymous conserved (PhyloP=0.431 with no splicing effect.
• BS2: High AC in GnomAd4 at 27 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
INHBB	NM_002193.4	c.720G>A	p.Glu240=	synonymous_variant	2/2	ENST00000295228.4	NP_002184.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INHBB	ENST00000295228.4	c.720G>A	p.Glu240=	synonymous_variant	2/2	1	NM_002193.4	ENSP00000295228	P1

Frequencies

GnomAD3 genomes AF: 0.000177 AC: 27 AN: 152212 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00308

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000458 AC: 115 AN: 251184 Hom.: 2 AF XY: 0.000405 AC XY: 55 AN XY: 135808

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00353

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000414

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000231 AC: 337 AN: 1461676 Hom.: 2 Cov.: 31 AF XY: 0.000205 AC XY: 149 AN XY: 727154

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00166

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000113

Gnomad4 NFE exome AF: 0.000211

Gnomad4 OTH exome AF: 0.000480

GnomAD4 genome AF: 0.000177 AC: 27 AN: 152330 Hom.: 0 Cov.: 33 AF XY: 0.000148 AC XY: 11 AN XY: 74488

Gnomad4 AFR AF: 0.0000240

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00309

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000147

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000141 Hom.: 0

Bravo AF: 0.000204

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000296

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	6.2
DANN	Benign	0.94

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: rs202216864; hg19: chr2-121106946;