7-41699543-G-C

Variant names:

• chr7-41699543-G-C
• rs3801158
• NM_002192.4:c.388+444C>G

Variant summary

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

The NM_002192.4(INHBA):​c.388+444C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.755 in 152,036 control chromosomes in the GnomAD database, including 43,809 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 0.75 (43809 hom., cov: 31)
• Consequence: INHBA NM_002192.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0640
• Publications: 3 publications found

Genes affected

INHBA (HGNC:6066): (inhibin subunit beta A) 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 the dimeric activin and inhibin protein complexes. These complexes activate and inhibit, respectively, follicle stimulating hormone secretion from the pituitary gland. The encoded protein also plays a role in eye, tooth and testis development. Elevated expression of this gene may be associated with cancer cachexia in human patients. [provided by RefSeq, Aug 2016]

INHBA-AS1 (HGNC:40303): (INHBA antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.808 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INHBA	NM_002192.4	c.388+444C>G		intron_variant	Intron 2 of 2	ENST00000242208.5	NP_002183.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INHBA	ENST00000242208.5	c.388+444C>G		intron_variant	Intron 2 of 2	1	NM_002192.4	ENSP00000242208.4

Frequencies

GnomAD3 genomes AF: 0.755 AC: 114676 AN: 151918 Hom.: 43792 Cov.: 31

Gnomad AFR AF: 0.697

Gnomad AMI AF: 0.834

Gnomad AMR AF: 0.633

Gnomad ASJ AF: 0.756

Gnomad EAS AF: 0.612

Gnomad SAS AF: 0.751

Gnomad FIN AF: 0.841

Gnomad MID AF: 0.742

Gnomad NFE AF: 0.814

Gnomad OTH AF: 0.750

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

GnomAD4 genome AF: 0.755 AC: 114732 AN: 152036 Hom.: 43809 Cov.: 31 AF XY: 0.751 AC XY: 55826 AN XY: 74300

African (AFR) AF: 0.697 AC: 28883 AN: 41438

American (AMR) AF: 0.633 AC: 9672 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.756 AC: 2623 AN: 3470

East Asian (EAS) AF: 0.613 AC: 3139 AN: 5124

South Asian (SAS) AF: 0.750 AC: 3620 AN: 4828

European-Finnish (FIN) AF: 0.841 AC: 8906 AN: 10584

Middle Eastern (MID) AF: 0.740 AC: 216 AN: 292

European-Non Finnish (NFE) AF: 0.814 AC: 55342 AN: 67998

Other (OTH) AF: 0.744 AC: 1570 AN: 2110

Alfa AF: 0.792 Hom.: 5964

Bravo AF: 0.729

Asia WGS AF: 0.684 AC: 2380 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	0.57
PhyloP100		-0.064
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: rs3801158; hg19: chr7-41739141;