12-57450266-C-T

Variant names:

• chr12-57450266-C-T
• rs3741414
• NM_005538.4:c.*244C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005538.4(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 NM_005538.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.530
• Publications: 73 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005538.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INHBC	NM_005538.4	MANE Select	c.*244C>T		3_prime_UTR	Exon 2 of 2	NP_005529.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INHBC	ENST00000309668.3	TSL:1 MANE Select	c.*244C>T		3_prime_UTR	Exon 2 of 2	ENSP00000308716.2

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

African (AFR) AF: 0.0901 AC: 604 AN: 6706

American (AMR) AF: 0.331 AC: 2503 AN: 7560

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 1252 AN: 8264

East Asian (EAS) AF: 0.0858 AC: 1609 AN: 18750

South Asian (SAS) AF: 0.0767 AC: 521 AN: 6794

European-Finnish (FIN) AF: 0.234 AC: 3904 AN: 16688

Middle Eastern (MID) AF: 0.0608 AC: 69 AN: 1134

European-Non Finnish (NFE) AF: 0.226 AC: 32589 AN: 144372

Other (OTH) AF: 0.182 AC: 2657 AN: 14564

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

African (AFR) AF: 0.0930 AC: 3859 AN: 41496

American (AMR) AF: 0.276 AC: 4213 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 554 AN: 3472

East Asian (EAS) AF: 0.0796 AC: 411 AN: 5166

South Asian (SAS) AF: 0.0817 AC: 393 AN: 4812

European-Finnish (FIN) AF: 0.231 AC: 2440 AN: 10580

Middle Eastern (MID) AF: 0.0479 AC: 14 AN: 292

European-Non Finnish (NFE) AF: 0.232 AC: 15735 AN: 67934

Other (OTH) AF: 0.169 AC: 356 AN: 2102

Alfa AF: 0.215 Hom.: 7948

Bravo AF: 0.194

Asia WGS AF: 0.105 AC: 367 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.3
DANN	Benign	0.43
PhyloP100		-0.53
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: rs3741414; hg19: chr12-57844049;