rs560048

Positions:

• chr12-57435346-C-T

Variant summary

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

The NM_005538.4(INHBC):​c.313+147C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.46 in 740,598 control chromosomes in the GnomAD database, including 81,610 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 0.43 (14785 hom., cov: 32)
  • Exomes 𝑓: 0.47 (66825 hom.)
• Consequence: INHBC NM_005538.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41

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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.498 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
INHBC	NM_005538.4	c.313+147C>T		intron_variant		ENST00000309668.3	NP_005529.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INHBC	ENST00000309668.3	c.313+147C>T		intron_variant		1	NM_005538.4	ENSP00000308716	P1

Frequencies

GnomAD3 genomes AF: 0.427 AC: 64939 AN: 151914 Hom.: 14764 Cov.: 32

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.473

Gnomad AMR AF: 0.506

Gnomad ASJ AF: 0.366

Gnomad EAS AF: 0.416

Gnomad SAS AF: 0.516

Gnomad FIN AF: 0.580

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.473

Gnomad OTH AF: 0.402

GnomAD4 exome AF: 0.468 AC: 275414 AN: 588566 Hom.: 66825 AF XY: 0.469 AC XY: 141906 AN XY: 302792

Gnomad4 AFR exome AF: 0.271

Gnomad4 AMR exome AF: 0.564

Gnomad4 ASJ exome AF: 0.361

Gnomad4 EAS exome AF: 0.401

Gnomad4 SAS exome AF: 0.514

Gnomad4 FIN exome AF: 0.560

Gnomad4 NFE exome AF: 0.471

Gnomad4 OTH exome AF: 0.444

GnomAD4 genome AF: 0.427 AC: 64990 AN: 152032 Hom.: 14785 Cov.: 32 AF XY: 0.434 AC XY: 32261 AN XY: 74334

Gnomad4 AFR AF: 0.282

Gnomad4 AMR AF: 0.507

Gnomad4 ASJ AF: 0.366

Gnomad4 EAS AF: 0.416

Gnomad4 SAS AF: 0.515

Gnomad4 FIN AF: 0.580

Gnomad4 NFE AF: 0.473

Gnomad4 OTH AF: 0.407

Alfa AF: 0.446 Hom.: 19665

Bravo AF: 0.416

Asia WGS AF: 0.454 AC: 1579 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.8
DANN	Benign	0.26

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: rs560048; hg19: chr12-57829129;