12-57450266-C-T

Position:

• chr12-57450266-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000309668.3(INHBC):​c.*244C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 376,874 control chromosomes in the GnomAD database, including 8,261 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 0.19 (3106 hom., cov: 32)
  • Exomes 𝑓: 0.20 (5155 hom.)
• Consequence: INHBC ENST00000309668.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.530

Genes affected

INHBC (HGNC:6068): (inhibin subunit beta C) 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 homodimeric and heterodimeric activin complexes. The heterodimeric complex may function in the inhibition of activin A signaling. Transgenic mice overexpressing this gene exhibit defects in testis, liver and prostate. [provided by RefSeq, Aug 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
INHBC	NM_005538.4	c.*244C>T		3_prime_UTR_variant	2/2	ENST00000309668.3	NP_005529.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INHBC	ENST00000309668.3	c.*244C>T		3_prime_UTR_variant	2/2	1	NM_005538.4	ENSP00000308716	P1

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28226 AN: 151924 Hom.: 3095 Cov.: 32

Gnomad AFR AF: 0.0931

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.0798

Gnomad SAS AF: 0.0822

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.0510

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.171

GnomAD4 exome AF: 0.203 AC: 45708 AN: 224832 Hom.: 5155 Cov.: 4 AF XY: 0.200 AC XY: 22707 AN XY: 113644

Gnomad4 AFR exome AF: 0.0901

Gnomad4 AMR exome AF: 0.331

Gnomad4 ASJ exome AF: 0.151

Gnomad4 EAS exome AF: 0.0858

Gnomad4 SAS exome AF: 0.0767

Gnomad4 FIN exome AF: 0.234

Gnomad4 NFE exome AF: 0.226

Gnomad4 OTH exome AF: 0.182

GnomAD4 genome AF: 0.186 AC: 28250 AN: 152042 Hom.: 3106 Cov.: 32 AF XY: 0.183 AC XY: 13584 AN XY: 74326

Gnomad4 AFR AF: 0.0930

Gnomad4 AMR AF: 0.276

Gnomad4 ASJ AF: 0.160

Gnomad4 EAS AF: 0.0796

Gnomad4 SAS AF: 0.0817

Gnomad4 FIN AF: 0.231

Gnomad4 NFE AF: 0.232

Gnomad4 OTH AF: 0.169

Alfa AF: 0.212 Hom.: 2587

Bravo AF: 0.194

Asia WGS AF: 0.105 AC: 367 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.3
DANN	Benign	0.43

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: rs3741414; hg19: chr12-57844049;