rs2741

Positions:

• chr7-30975950-T-G

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.974+82T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 818,968 control chromosomes in the GnomAD database, including 5,654 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (922 hom., cov: 32)
  • Exomes 𝑓: 0.11 (4732 hom.)
• Consequence: GHRHR NM_000823.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.609

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 7-30975950-T-G is Benign according to our data. Variant chr7-30975950-T-G is described in ClinVar as [Benign]. Clinvar id is 1221455.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GHRHR	NM_000823.4	c.974+82T>G		intron_variant		ENST00000326139.7	NP_000814.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GHRHR	ENST00000326139.7	c.974+82T>G		intron_variant		1	NM_000823.4	ENSP00000320180.2

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16122 AN: 152058 Hom.: 927 Cov.: 32

Gnomad AFR AF: 0.0894

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.0797

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.128

GnomAD4 exome AF: 0.114 AC: 76299 AN: 666792 Hom.: 4732 Cov.: 8 AF XY: 0.115 AC XY: 41502 AN XY: 359586

Gnomad4 AFR exome AF: 0.0904

Gnomad4 AMR exome AF: 0.135

Gnomad4 ASJ exome AF: 0.164

Gnomad4 EAS exome AF: 0.212

Gnomad4 SAS exome AF: 0.133

Gnomad4 FIN exome AF: 0.0804

Gnomad4 NFE exome AF: 0.102

Gnomad4 OTH exome AF: 0.117

GnomAD4 genome AF: 0.106 AC: 16108 AN: 152176 Hom.: 922 Cov.: 32 AF XY: 0.105 AC XY: 7806 AN XY: 74396

Gnomad4 AFR AF: 0.0893

Gnomad4 AMR AF: 0.126

Gnomad4 ASJ AF: 0.165

Gnomad4 EAS AF: 0.186

Gnomad4 SAS AF: 0.142

Gnomad4 FIN AF: 0.0797

Gnomad4 NFE AF: 0.103

Gnomad4 OTH AF: 0.128

Alfa AF: 0.108 Hom.: 1138

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	-0.90
CADD	Benign	4.3
DANN	Benign	0.73

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

Other links and lift over

dbSNP: rs2741; hg19: chr7-31015565; COSMIC: COSV58195915; COSMIC: COSV58195915;