Variant 7-30976403-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000823.4(GHRHR):c.975-26G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 1,606,386 control chromosomes in the GnomAD database, including 9,664 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.11 ( 913 hom., cov: 32)

Exomes 𝑓: 0.11 ( 8751 hom. )

Consequence

GHRHR
NM_000823.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.447

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:

GHRHR (HGNC:):

GHRHR links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

This place is a probable branch point but likely benign (scored 1 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 7-30976403-G-A is Benign according to our data. Variant chr7-30976403-G-A is described in ClinVar as [Benign]. Clinvar id is 1226509.Status of the report is criteria_provided_single_submitter, 1 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	Protein	UniProt
GHRHR	NM_000823.4 linkuse as main transcript	c.975-26G>A		intron_variant		ENST00000326139.7	NP_000814.2	Q02643A0A090N8Y6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GHRHR	ENST00000326139.7 linkuse as main transcript	c.975-26G>A		intron_variant		1	NM_000823.4	ENSP00000320180.2		Q02643

Frequencies

GnomAD3 genomes

AF:

0.106

AC:

16056

AN:

152040

Hom.:

918

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0892

Gnomad AMI

AF:

0.116

Gnomad AMR

AF:

0.125

Gnomad ASJ

AF:

0.164

Gnomad EAS

AF:

0.184

Gnomad SAS

AF:

0.143

Gnomad FIN

AF:

0.0800

Gnomad MID

AF:

0.196

Gnomad NFE

AF:

0.102

Gnomad OTH

AF:

0.127

GnomAD3 exomes

AF:

0.116

AC:

29055

AN:

251018

Hom.:

1800

AF XY:

0.115

AC XY:

15648

AN XY:

135700

show subpopulations

Gnomad AFR exome

AF:

0.0861

Gnomad AMR exome

AF:

0.130

Gnomad ASJ exome

AF:

0.164

Gnomad EAS exome

AF:

0.182

Gnomad SAS exome

AF:

0.135

Gnomad FIN exome

AF:

0.0803

Gnomad NFE exome

AF:

0.101

Gnomad OTH exome

AF:

0.129

GnomAD4 exome

AF:

0.106

AC:

154043

AN:

1454228

Hom.:

8751

Cov.:

AF XY:

0.107

AC XY:

77555

AN XY:

723876

show subpopulations

Gnomad4 AFR exome

AF:

0.0897

Gnomad4 AMR exome

AF:

0.134

Gnomad4 ASJ exome

AF:

0.164

Gnomad4 EAS exome

AF:

0.207

Gnomad4 SAS exome

AF:

0.132

Gnomad4 FIN exome

AF:

0.0797

Gnomad4 NFE exome

AF:

0.0987

Gnomad4 OTH exome

AF:

0.114

GnomAD4 genome

AF:

0.105

AC:

16042

AN:

152158

Hom.:

913

Cov.:

AF XY:

0.105

AC XY:

7775

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.0892

Gnomad4 AMR

AF:

0.125

Gnomad4 ASJ

AF:

0.164

Gnomad4 EAS

AF:

0.183

Gnomad4 SAS

AF:

0.140

Gnomad4 FIN

AF:

0.0800

Gnomad4 NFE

AF:

0.102

Gnomad4 OTH

AF:

0.127

Alfa

AF:

0.0951

Hom.:

395

Bravo

AF:

0.111

Asia WGS

AF:

0.149

AC:

518

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

DANN

Benign

0.77

BranchPoint Hunter

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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