12-57442182-C-T

Variant names:

• chr12-57442182-C-T
• rs2943693
• NM_005538.4:c.313+6983C>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.313+6983C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 152,140 control chromosomes in the GnomAD database, including 4,504 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 0.23 (4504 hom., cov: 31)
• Consequence: INHBC NM_005538.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.354
• Publications: 6 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=-0.99).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INHBC	NM_005538.4	c.313+6983C>T		intron_variant	Intron 1 of 1	ENST00000309668.3	NP_005529.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INHBC	ENST00000309668.3	c.313+6983C>T		intron_variant	Intron 1 of 1	1	NM_005538.4	ENSP00000308716.2

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35454 AN: 152022 Hom.: 4497 Cov.: 31

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.335

Gnomad SAS AF: 0.433

Gnomad FIN AF: 0.350

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.225

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

GnomAD4 genome AF: 0.233 AC: 35476 AN: 152140 Hom.: 4504 Cov.: 31 AF XY: 0.243 AC XY: 18076 AN XY: 74372

African (AFR) AF: 0.162 AC: 6715 AN: 41516

American (AMR) AF: 0.225 AC: 3445 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.206 AC: 715 AN: 3472

East Asian (EAS) AF: 0.335 AC: 1736 AN: 5176

South Asian (SAS) AF: 0.433 AC: 2090 AN: 4828

European-Finnish (FIN) AF: 0.350 AC: 3699 AN: 10568

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.241 AC: 16401 AN: 67978

Other (OTH) AF: 0.231 AC: 487 AN: 2112

Alfa AF: 0.233 Hom.: 1065

Bravo AF: 0.213

Asia WGS AF: 0.348 AC: 1208 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	4.8
DANN	Benign	0.42
PhyloP100		0.35
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: rs2943693; hg19: chr12-57835965;