NM_005538.4:c.70G>T

Variant names:

• chr12-57434956-G-T
• rs140503654
• NM_005538.4:c.70G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_005538.4(INHBC):​c.70G>T​(p.Gly24Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000329 in 152,198 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G24S) has been classified as Likely benign.

• Frequency: Genomes: 𝑓 0.000033 (0 hom., cov: 32)
• Consequence: INHBC NM_005538.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.90
• Publications: 1 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.24576157).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INHBC	NM_005538.4	MANE Select	c.70G>T	p.Gly24Cys	missense	Exon 1 of 2	NP_005529.1	P55103

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INHBC	ENST00000309668.3	TSL:1 MANE Select	c.70G>T	p.Gly24Cys	missense	Exon 1 of 2	ENSP00000308716.2	P55103

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152198 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152198 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74354

African (AFR) AF: 0.00 AC: 0 AN: 41448

American (AMR) AF: 0.000327 AC: 5 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000302

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	2.2
DANN	Uncertain	0.98
DEOGEN2	Benign	0.30	T
Eigen	Benign	-0.84
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.049	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.075	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.31	T
MutationAssessor	Benign	2.0	M
PhyloP100		-1.9
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.5	N
REVEL	Uncertain	0.40
Sift	Benign	0.086	T
Sift4G	Benign	0.093	T
Polyphen		0.98	D
Vest4		0.21
MutPred		0.43		Gain of catalytic residue at A22 (P = 0)
MVP		0.70
MPC		0.69
ClinPred		0.56	D
GERP RS		-7.2
PromoterAI		-0.0054	Neutral
Varity_R		0.091
gMVP		0.36
Mutation Taster		=91/9	polymorphism

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: rs140503654; hg19: chr12-57828739;