rs11770488

Variant names:

• chr7-41693256-T-A
• rs11770488
• NM_002192.4:c.389-2714A>T

Variant summary

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

The NM_002192.4(INHBA):​c.389-2714A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 152,026 control chromosomes in the GnomAD database, including 1,385 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 0.11 (1385 hom., cov: 32)
• Consequence: INHBA NM_002192.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.823
• Publications: 4 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INHBA	NM_002192.4	c.389-2714A>T		intron_variant	Intron 2 of 2	ENST00000242208.5	NP_002183.1
INHBA	XM_017012174.2	c.389-2714A>T		intron_variant	Intron 2 of 2		XP_016867663.2
INHBA	XM_047420335.1	c.389-2714A>T		intron_variant	Intron 3 of 3		XP_047276291.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INHBA	ENST00000242208.5	c.389-2714A>T		intron_variant	Intron 2 of 2	1	NM_002192.4	ENSP00000242208.4
INHBA	ENST00000442711.1	c.389-2714A>T		intron_variant	Intron 1 of 1	1		ENSP00000397197.1
INHBA	ENST00000638023.1	c.389-2714A>T		intron_variant	Intron 4 of 4	5		ENSP00000490646.1
INHBA	ENST00000416150.1	n.52+12028A>T		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16908 AN: 151910 Hom.: 1384 Cov.: 32

Gnomad AFR AF: 0.0283

Gnomad AMI AF: 0.0779

Gnomad AMR AF: 0.0720

Gnomad ASJ AF: 0.0698

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0638

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.0953

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

GnomAD4 genome AF: 0.111 AC: 16905 AN: 152026 Hom.: 1385 Cov.: 32 AF XY: 0.111 AC XY: 8251 AN XY: 74300

African (AFR) AF: 0.0282 AC: 1170 AN: 41492

American (AMR) AF: 0.0718 AC: 1097 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0698 AC: 242 AN: 3466

East Asian (EAS) AF: 0.00155 AC: 8 AN: 5168

South Asian (SAS) AF: 0.0649 AC: 313 AN: 4822

European-Finnish (FIN) AF: 0.228 AC: 2404 AN: 10552

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.167 AC: 11372 AN: 67924

Other (OTH) AF: 0.0938 AC: 198 AN: 2110

Alfa AF: 0.134 Hom.: 217

Bravo AF: 0.0948

Asia WGS AF: 0.0330 AC: 116 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	9.2
DANN	Benign	0.74
PhyloP100		0.82
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: rs11770488; hg19: chr7-41732854;