2-120346181-G-A

Position:

• chr2-120346181-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_002193.4(INHBB):​c.-8G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00944 in 1,169,920 control chromosomes in the GnomAD database, including 72 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0072 (11 hom., cov: 32)
  • Exomes 𝑓: 0.0098 (61 hom.)
• Consequence: INHBB NM_002193.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.464

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 2-120346181-G-A is Benign according to our data. Variant chr2-120346181-G-A is described in ClinVar as [Benign]. Clinvar id is 2651314.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 1074 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
INHBB	NM_002193.4	c.-8G>A		5_prime_UTR_variant	1/2	ENST00000295228.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INHBB	ENST00000295228.4	c.-8G>A		5_prime_UTR_variant	1/2	1	NM_002193.4	P1

Frequencies

GnomAD3 genomes AF: 0.00724 AC: 1073 AN: 148144 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.00156

Gnomad AMI AF: 0.0989

Gnomad AMR AF: 0.00141

Gnomad ASJ AF: 0.000882

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00229

Gnomad FIN AF: 0.0132

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0114

Gnomad OTH AF: 0.00147

GnomAD4 exome AF: 0.00976 AC: 9973 AN: 1021690 Hom.: 61 Cov.: 31 AF XY: 0.00970 AC XY: 4668 AN XY: 481120

Gnomad4 AFR exome AF: 0.00107

Gnomad4 AMR exome AF: 0.00200

Gnomad4 ASJ exome AF: 0.00258

Gnomad4 EAS exome AF: 0.000192

Gnomad4 SAS exome AF: 0.00311

Gnomad4 FIN exome AF: 0.0116

Gnomad4 NFE exome AF: 0.0106

Gnomad4 OTH exome AF: 0.00748

GnomAD4 genome AF: 0.00725 AC: 1074 AN: 148230 Hom.: 11 Cov.: 32 AF XY: 0.00714 AC XY: 516 AN XY: 72250

Gnomad4 AFR AF: 0.00156

Gnomad4 AMR AF: 0.00140

Gnomad4 ASJ AF: 0.000882

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00229

Gnomad4 FIN AF: 0.0132

Gnomad4 NFE AF: 0.0114

Gnomad4 OTH AF: 0.00146

Alfa AF: 0.00577 Hom.: 0

Bravo AF: 0.00619

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

INHBB: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	18
DANN	Benign	0.89

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: rs1002875809; hg19: chr2-121103757;