rs4988494

Positions:

• chr7-30964204-C-T

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.57+79C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 1,275,884 control chromosomes in the GnomAD database, including 15,587 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.18 (3301 hom., cov: 33)
  • Exomes 𝑓: 0.13 (12286 hom.)
• Consequence: GHRHR NM_000823.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.93

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: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 7-30964204-C-T is Benign according to our data. Variant chr7-30964204-C-T is described in ClinVar as [Benign]. Clinvar id is 1182916.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GHRHR	NM_000823.4	c.57+79C>T		intron_variant		ENST00000326139.7	NP_000814.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GHRHR	ENST00000326139.7	c.57+79C>T		intron_variant		1	NM_000823.4	ENSP00000320180.2
GHRHR	ENST00000466427.1	n.285-4630C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.184 AC: 27980 AN: 152076 Hom.: 3286 Cov.: 33

Gnomad AFR AF: 0.319

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.243

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.0821

Gnomad MID AF: 0.290

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.205

GnomAD4 exome AF: 0.131 AC: 147533 AN: 1123690 Hom.: 12286 AF XY: 0.137 AC XY: 77463 AN XY: 566402

Gnomad4 AFR exome AF: 0.331

Gnomad4 AMR exome AF: 0.148

Gnomad4 ASJ exome AF: 0.244

Gnomad4 EAS exome AF: 0.224

Gnomad4 SAS exome AF: 0.288

Gnomad4 FIN exome AF: 0.0795

Gnomad4 NFE exome AF: 0.103

Gnomad4 OTH exome AF: 0.162

GnomAD4 genome AF: 0.184 AC: 28028 AN: 152194 Hom.: 3301 Cov.: 33 AF XY: 0.186 AC XY: 13857 AN XY: 74426

Gnomad4 AFR AF: 0.319

Gnomad4 AMR AF: 0.172

Gnomad4 ASJ AF: 0.243

Gnomad4 EAS AF: 0.243

Gnomad4 SAS AF: 0.289

Gnomad4 FIN AF: 0.0821

Gnomad4 NFE AF: 0.106

Gnomad4 OTH AF: 0.206

Alfa AF: 0.132 Hom.: 2153

Bravo AF: 0.194

Asia WGS AF: 0.248 AC: 862 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

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.094
DANN	Benign	0.60

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: rs4988494; hg19: chr7-31003819; COSMIC: COSV58196070;