chr7-30977488-G-C

Variant names:

• chr7-30977488-G-C
• rs4988505
• NM_000823.4:c.1146+166G>C

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.1146+166G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 152,070 control chromosomes in the GnomAD database, including 9,824 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.34 (9824 hom., cov: 32)
• Consequence: GHRHR NM_000823.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.239
• Publications: 5 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=-0.47).
• BP6: Variant 7-30977488-G-C is Benign according to our data. Variant chr7-30977488-G-C is described in ClinVar as Benign. ClinVar VariationId is 1259484.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.491 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GHRHR	NM_000823.4	MANE Select	c.1146+166G>C		intron	N/A	NP_000814.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GHRHR	ENST00000326139.7	TSL:1 MANE Select	c.1146+166G>C		intron	N/A	ENSP00000320180.2
	GHRHR	ENST00000409904.7	TSL:1	c.954+166G>C		intron	N/A	ENSP00000387113.3
	GHRHR	ENST00000409316.5	TSL:1	c.445+166G>C		intron	N/A	ENSP00000386602.1

Frequencies

GnomAD3 genomes AF: 0.341 AC: 51833 AN: 151950 Hom.: 9786 Cov.: 32

Gnomad AFR AF: 0.496

Gnomad AMI AF: 0.328

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.0350

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.268

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.296

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.341 AC: 51926 AN: 152070 Hom.: 9824 Cov.: 32 AF XY: 0.337 AC XY: 25088 AN XY: 74350

African (AFR) AF: 0.497 AC: 20591 AN: 41460

American (AMR) AF: 0.247 AC: 3772 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.212 AC: 733 AN: 3460

East Asian (EAS) AF: 0.0349 AC: 181 AN: 5184

South Asian (SAS) AF: 0.300 AC: 1442 AN: 4810

European-Finnish (FIN) AF: 0.303 AC: 3203 AN: 10588

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.309 AC: 21001 AN: 67982

Other (OTH) AF: 0.298 AC: 627 AN: 2104

Alfa AF: 0.172 Hom.: 322

Bravo AF: 0.339

Asia WGS AF: 0.214 AC: 746 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	10
DANN	Benign	0.77
PhyloP100		0.24
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4988505; hg19: chr7-31017103; COSMIC: COSV58195931; COSMIC: COSV58195931;