Variant 7-30964024-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000823.4(GHRHR):c.-45C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.034 in 1,526,688 control chromosomes in the GnomAD database, including 2,333 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.067 ( 652 hom., cov: 33)

Exomes 𝑓: 0.030 ( 1681 hom. )

Consequence

GHRHR
NM_000823.4 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.749

Variant links:

Genes affected

GHRHR (HGNC:4266): (growth hormone releasing hormone receptor) This gene encodes a receptor for growth hormone-releasing hormone. Binding of this hormone to the receptor leads to synthesis and release of growth hormone. Mutations in this gene have been associated with isolated growth hormone deficiency (IGHD), also known as Dwarfism of Sindh, a disorder characterized by short stature. [provided by RefSeq, Jun 2010]

GHRHR links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 7-30964024-C-T is Benign according to our data. Variant chr7-30964024-C-T is described in ClinVar as [Benign]. Clinvar id is 360026.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GHRHR	NM_000823.4 linkuse as main transcript	c.-45C>T		5_prime_UTR_variant	1/13	ENST00000326139.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GHRHR	ENST00000326139.7 linkuse as main transcript	c.-45C>T		5_prime_UTR_variant	1/13	1	NM_000823.4	P1
GHRHR	ENST00000466427.1 linkuse as main transcript	n.285-4810C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0672

AC:

10227

AN:

152156

Hom.:

653

Cov.:

show subpopulations

Gnomad AFR

AF:

0.151

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.0584

Gnomad ASJ

AF:

0.0253

Gnomad EAS

AF:

0.184

Gnomad SAS

AF:

0.0906

Gnomad FIN

AF:

0.0259

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0172

Gnomad OTH

AF:

0.0626

GnomAD3 exomes

AF:

0.0562

AC:

8692

AN:

154790

Hom.:

439

AF XY:

0.0552

AC XY:

4507

AN XY:

81598

show subpopulations

Gnomad AFR exome

AF:

0.152

Gnomad AMR exome

AF:

0.0702

Gnomad ASJ exome

AF:

0.0241

Gnomad EAS exome

AF:

0.173

Gnomad SAS exome

AF:

0.0820

Gnomad FIN exome

AF:

0.0240

Gnomad NFE exome

AF:

0.0179

Gnomad OTH exome

AF:

0.0438

GnomAD4 exome

AF:

0.0304

AC:

41719

AN:

1374414

Hom.:

1681

Cov.:

AF XY:

0.0315

AC XY:

21419

AN XY:

679484

show subpopulations

Gnomad4 AFR exome

AF:

0.160

Gnomad4 AMR exome

AF:

0.0697

Gnomad4 ASJ exome

AF:

0.0248

Gnomad4 EAS exome

AF:

0.175

Gnomad4 SAS exome

AF:

0.0814

Gnomad4 FIN exome

AF:

0.0250

Gnomad4 NFE exome

AF:

0.0163

Gnomad4 OTH exome

AF:

0.0399

GnomAD4 genome

AF:

0.0672

AC:

10234

AN:

152274

Hom.:

652

Cov.:

AF XY:

0.0692

AC XY:

5150

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.151

Gnomad4 AMR

AF:

0.0584

Gnomad4 ASJ

AF:

0.0253

Gnomad4 EAS

AF:

0.184

Gnomad4 SAS

AF:

0.0900

Gnomad4 FIN

AF:

0.0259

Gnomad4 NFE

AF:

0.0172

Gnomad4 OTH

AF:

0.0624

Alfa

AF:

0.0302

Hom.:

195

Bravo

AF:

0.0748

Asia WGS

AF:

0.116

AC:

404

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Isolated growth hormone deficiency type IB

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

3.9

DANN

Benign

0.55

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over