rs4988494

Variant names:

• chr7-30964204-C-T
• rs4988494
• NM_000823.4:c.57+79C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-30964204-C-T
• chr7-30964204-C-A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000823.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GHRHR	NM_000823.4	MANE Select	c.57+79C>T		intron	N/A	NP_000814.2	A0A090N8Y6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GHRHR	ENST00000326139.7	TSL:1 MANE Select	c.57+79C>T		intron	N/A	ENSP00000320180.2	Q02643
	GHRHR	ENST00000466427.1	TSL:5	n.285-4630C>T		intron	N/A

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

African (AFR) AF: 0.331 AC: 8812 AN: 26610

American (AMR) AF: 0.148 AC: 5241 AN: 35408

Ashkenazi Jewish (ASJ) AF: 0.244 AC: 5744 AN: 23544

East Asian (EAS) AF: 0.224 AC: 7752 AN: 34586

South Asian (SAS) AF: 0.288 AC: 21360 AN: 74206

European-Finnish (FIN) AF: 0.0795 AC: 2889 AN: 36318

Middle Eastern (MID) AF: 0.288 AC: 1086 AN: 3774

European-Non Finnish (NFE) AF: 0.103 AC: 86671 AN: 840078

Other (OTH) AF: 0.162 AC: 7978 AN: 49166

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

African (AFR) AF: 0.319 AC: 13248 AN: 41496

American (AMR) AF: 0.172 AC: 2628 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 842 AN: 3470

East Asian (EAS) AF: 0.243 AC: 1255 AN: 5168

South Asian (SAS) AF: 0.289 AC: 1397 AN: 4830

European-Finnish (FIN) AF: 0.0821 AC: 872 AN: 10618

Middle Eastern (MID) AF: 0.281 AC: 82 AN: 292

European-Non Finnish (NFE) AF: 0.106 AC: 7185 AN: 68004

Other (OTH) AF: 0.206 AC: 435 AN: 2108

Alfa AF: 0.136 Hom.: 2984

Bravo AF: 0.194

Asia WGS AF: 0.248 AC: 862 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.094
DANN	Benign	0.60
PhyloP100		-1.9
PromoterAI		0.0021	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs4988494;

hg19: chr7-31003819;

COSMIC: COSV58196070;