rs73100934

Variant names:

• chr7-41703060-T-C
• rs73100934
• NM_002192.4:c.-199A>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.-199A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0553 in 152,338 control chromosomes in the GnomAD database, including 328 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 0.055 (327 hom., cov: 32)
  • Exomes 𝑓: 0.22 (1 hom.)
• Consequence: INHBA NM_002192.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.531
• 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]

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=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0807 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002192.4. 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
	INHBA	NM_002192.4	MANE Select	c.-199A>G		5_prime_UTR	Exon 1 of 3	NP_002183.1
	INHBA-AS1	NR_027118.2		n.171-7538T>C		intron	N/A
	INHBA-AS1	NR_027119.2		n.171-7538T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INHBA	ENST00000242208.5	TSL:1 MANE Select	c.-199A>G		5_prime_UTR	Exon 1 of 3	ENSP00000242208.4
	INHBA-AS1	ENST00000415848.6	TSL:1	n.174-7538T>C		intron	N/A
	INHBA-AS1	ENST00000420821.2	TSL:1	n.161-7538T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0553 AC: 8424 AN: 152202 Hom.: 328 Cov.: 32

Gnomad AFR AF: 0.0156

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.0681

Gnomad ASJ AF: 0.0603

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0250

Gnomad FIN AF: 0.0549

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0825

Gnomad OTH AF: 0.0611

GnomAD4 exome AF: 0.222 AC: 4 AN: 18 Hom.: 1 Cov.: 0 AF XY: 0.286 AC XY: 4 AN XY: 14

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.250 AC: 4 AN: 16

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0553 AC: 8424 AN: 152320 Hom.: 327 Cov.: 32 AF XY: 0.0539 AC XY: 4015 AN XY: 74500

African (AFR) AF: 0.0155 AC: 646 AN: 41570

American (AMR) AF: 0.0682 AC: 1043 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0603 AC: 209 AN: 3468

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5184

South Asian (SAS) AF: 0.0251 AC: 121 AN: 4828

European-Finnish (FIN) AF: 0.0549 AC: 583 AN: 10618

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0825 AC: 5615 AN: 68026

Other (OTH) AF: 0.0605 AC: 128 AN: 2116

Alfa AF: 0.0684 Hom.: 153

Bravo AF: 0.0555

Asia WGS AF: 0.0150 AC: 52 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	15
DANN	Benign	0.81
PhyloP100		0.53
PromoterAI		-0.0081	Neutral
Mutation Taster		=300/0	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: rs73100934; hg19: chr7-41742658;