rs45624437

Positions:

• chr2-120350606-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_002193.4(INHBB):​c.*732T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0107 in 148,940 control chromosomes in the GnomAD database, including 20 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 0.011 (20 hom., cov: 33)
  • Exomes 𝑓: 0.0094 (0 hom.)
• Consequence: INHBB NM_002193.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.812

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 (BayesDel_noAF=-0.84).
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0107 (1590/148834) while in subpopulation AMR AF= 0.0244 (365/14952). AF 95% confidence interval is 0.0223. There are 20 homozygotes in gnomad4. There are 837 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1590 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
INHBB	NM_002193.4	c.*732T>C		3_prime_UTR_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.*732T>C		3_prime_UTR_variant	2/2	1	NM_002193.4	ENSP00000295228.3

Frequencies

GnomAD3 genomes AF: 0.0107 AC: 1590 AN: 148722 Hom.: 20 Cov.: 33

Gnomad AFR AF: 0.00227

Gnomad AMI AF: 0.0210

Gnomad AMR AF: 0.0244

Gnomad ASJ AF: 0.000580

Gnomad EAS AF: 0.000395

Gnomad SAS AF: 0.00234

Gnomad FIN AF: 0.0391

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0103

Gnomad OTH AF: 0.00740

GnomAD4 exome AF: 0.00943 AC: 1 AN: 106 Hom.: 0 Cov.: 0 AF XY: 0.0200 AC XY: 1 AN XY: 50

Gnomad4 AFR exome AF: 0.00

Gnomad4 FIN exome AF: 0.0217

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0107 AC: 1590 AN: 148834 Hom.: 20 Cov.: 33 AF XY: 0.0115 AC XY: 837 AN XY: 72484

Gnomad4 AFR AF: 0.00226

Gnomad4 AMR AF: 0.0244

Gnomad4 ASJ AF: 0.000580

Gnomad4 EAS AF: 0.000396

Gnomad4 SAS AF: 0.00235

Gnomad4 FIN AF: 0.0391

Gnomad4 NFE AF: 0.0103

Gnomad4 OTH AF: 0.00732

Alfa AF: 0.0117 Hom.: 1

Bravo AF: 0.0105

Asia WGS AF: 0.000866 AC: 4 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	10
DANN	Benign	0.79

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: rs45624437; hg19: chr2-121108182;