rs4988504

Positions:

• chr7-30976403-G-A
• chr7-30976403-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.447

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]

ACMG classification

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	UniProt
GHRHR	NM_000823.4	c.975-26G>A		intron_variant		ENST00000326139.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GHRHR	ENST00000326139.7	c.975-26G>A		intron_variant		1	NM_000823.4	P1

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16056 AN: 152040 Hom.: 918 Cov.: 32

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

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.: 30 AF XY: 0.107 AC XY: 77555 AN XY: 723876

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.: 32 AF XY: 0.105 AC XY: 7775 AN XY: 74388

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

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	12
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

Other links and lift over

dbSNP: rs4988504; hg19: chr7-31016018; COSMIC: COSV58195924; COSMIC: COSV58195924;