chr7-30964097-T-A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000823.4(GHRHR):​c.29T>A​(p.Val10Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,397,896 control chromosomes in the GnomAD database, with no homozygous occurrence. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V10I) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

GHRHR
NM_000823.4 missense

Scores

4
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.904

Publications

5 publications found
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 Gene-Disease associations (from GenCC):
  • isolated growth hormone deficiency type IB
    Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Laboratory for Molecular Medicine, Orphanet
  • isolated growth hormone deficiency, type 4
    Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GHRHRNM_000823.4 linkc.29T>A p.Val10Asp missense_variant Exon 1 of 13 ENST00000326139.7 NP_000814.2 Q02643A0A090N8Y6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GHRHRENST00000326139.7 linkc.29T>A p.Val10Asp missense_variant Exon 1 of 13 1 NM_000823.4 ENSP00000320180.2 Q02643
GHRHRENST00000466427.1 linkn.285-4737T>A intron_variant Intron 1 of 1 5

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD2 exomes
AF:
0.00000646
AC:
1
AN:
154880
AF XY:
0.0000123
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
7.15e-7
AC:
1
AN:
1397896
Hom.:
0
Cov.:
32
AF XY:
0.00000145
AC XY:
1
AN XY:
689522
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
31590
American (AMR)
AF:
0.00
AC:
0
AN:
35704
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25182
East Asian (EAS)
AF:
0.00
AC:
0
AN:
35738
South Asian (SAS)
AF:
0.0000126
AC:
1
AN:
79230
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
47924
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5612
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1078944
Other (OTH)
AF:
0.00
AC:
0
AN:
57972
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.18
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.35
CADD
Benign
17
DANN
Benign
0.91
DEOGEN2
Benign
0.40
T
Eigen
Benign
-0.61
Eigen_PC
Benign
-0.76
FATHMM_MKL
Benign
0.17
N
LIST_S2
Benign
0.48
T
M_CAP
Benign
0.019
T
MetaRNN
Uncertain
0.69
D
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.8
L
PhyloP100
0.90
PrimateAI
Benign
0.39
T
PROVEAN
Uncertain
-2.4
N
REVEL
Benign
0.16
Sift
Uncertain
0.0010
D
Sift4G
Uncertain
0.041
D
Polyphen
0.81
P
Vest4
0.55
MutPred
0.63
Loss of sheet (P = 0.0037);
MVP
0.35
MPC
0.28
ClinPred
0.20
T
GERP RS
-0.24
PromoterAI
-0.015
Neutral
Varity_R
0.39
gMVP
0.65
Mutation Taster
=55/45
polymorphism

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

Other links and lift over

dbSNP: rs139599160; hg19: chr7-31003712; API