rs533975

Variant names:

• chr12-57438201-G-A
• rs533975
• NM_005538.4:c.313+3002G>A

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+3002G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 151,968 control chromosomes in the GnomAD database, including 14,775 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 (14775 hom., cov: 32)
• Consequence: INHBC NM_005538.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.309
• Publications: 4 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=-0.51).
• 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 rank	MANE	Protein	UniProt
INHBC	NM_005538.4	c.313+3002G>A		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+3002G>A		intron_variant	Intron 1 of 1	1	NM_005538.4	ENSP00000308716.2

Frequencies

GnomAD3 genomes AF: 0.428 AC: 64921 AN: 151850 Hom.: 14753 Cov.: 32

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.506

Gnomad ASJ AF: 0.366

Gnomad EAS AF: 0.418

Gnomad SAS AF: 0.516

Gnomad FIN AF: 0.580

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.473

Gnomad OTH AF: 0.403

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

GnomAD4 genome AF: 0.428 AC: 64975 AN: 151968 Hom.: 14775 Cov.: 32 AF XY: 0.434 AC XY: 32259 AN XY: 74266

African (AFR) AF: 0.283 AC: 11719 AN: 41456

American (AMR) AF: 0.507 AC: 7732 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.366 AC: 1269 AN: 3468

East Asian (EAS) AF: 0.418 AC: 2165 AN: 5180

South Asian (SAS) AF: 0.515 AC: 2482 AN: 4816

European-Finnish (FIN) AF: 0.580 AC: 6116 AN: 10540

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.473 AC: 32155 AN: 67946

Other (OTH) AF: 0.407 AC: 858 AN: 2108

Alfa AF: 0.426 Hom.: 2696

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	-0.51
CADD	Benign	6.6
DANN	Benign	0.83
PhyloP100		-0.31
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: rs533975; hg19: chr12-57831984;