chr2-120348427-A-G

Variant names:

• chr2-120348427-A-G
• rs11902591
• NM_002193.4:c.449-672A>G

Variant summary

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

Score: -12 - Benign

-12

BP4_StrongBA1

The NM_002193.4(INHBB):​c.449-672A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 151,866 control chromosomes in the GnomAD database, including 1,537 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 0.12 (1537 hom., cov: 29)
• Consequence: INHBB NM_002193.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.738
• Publications: 7 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 (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INHBB	NM_002193.4	c.449-672A>G		intron_variant	Intron 1 of 1	ENST00000295228.4	NP_002184.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INHBB	ENST00000295228.4	c.449-672A>G		intron_variant	Intron 1 of 1	1	NM_002193.4	ENSP00000295228.3

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17632 AN: 151748 Hom.: 1533 Cov.: 29

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.0664

Gnomad EAS AF: 0.462

Gnomad SAS AF: 0.0674

Gnomad FIN AF: 0.0858

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0688

Gnomad OTH AF: 0.0932

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.116 AC: 17651 AN: 151866 Hom.: 1537 Cov.: 29 AF XY: 0.120 AC XY: 8889 AN XY: 74210

African (AFR) AF: 0.145 AC: 5990 AN: 41386

American (AMR) AF: 0.186 AC: 2835 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.0664 AC: 230 AN: 3466

East Asian (EAS) AF: 0.462 AC: 2372 AN: 5134

South Asian (SAS) AF: 0.0672 AC: 324 AN: 4818

European-Finnish (FIN) AF: 0.0858 AC: 904 AN: 10538

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0688 AC: 4676 AN: 67972

Other (OTH) AF: 0.0960 AC: 202 AN: 2104

Alfa AF: 0.0876 Hom.: 1497

Bravo AF: 0.131

Asia WGS AF: 0.228 AC: 792 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	14
DANN	Benign	0.82
PhyloP100		0.74
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: rs11902591; hg19: chr2-121106003;