7-30955296-T-G

Variant names:

• chr7-30955296-T-G
• rs4723034
• ENST00000466427.1:n.285-13538T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000466427.1(GHRHR):​n.285-13538T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 152,012 control chromosomes in the GnomAD database, including 13,360 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.35 (13360 hom., cov: 32)
• Consequence: GHRHR ENST00000466427.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.308
• Publications: 2 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: Orphanet, Laboratory for Molecular Medicine
• isolated growth hormone deficiency, type 4

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.705 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000466427.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GHRHR	ENST00000466427.1	TSL:5	n.285-13538T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52420 AN: 151894 Hom.: 13303 Cov.: 32

Gnomad AFR AF: 0.711

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.319

Gnomad ASJ AF: 0.179

Gnomad EAS AF: 0.407

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.229

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.311

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

GnomAD4 genome AF: 0.346 AC: 52538 AN: 152012 Hom.: 13360 Cov.: 32 AF XY: 0.349 AC XY: 25944 AN XY: 74302

African (AFR) AF: 0.712 AC: 29506 AN: 41440

American (AMR) AF: 0.320 AC: 4886 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.179 AC: 621 AN: 3470

East Asian (EAS) AF: 0.406 AC: 2101 AN: 5176

South Asian (SAS) AF: 0.336 AC: 1619 AN: 4820

European-Finnish (FIN) AF: 0.229 AC: 2424 AN: 10582

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.155 AC: 10554 AN: 67940

Other (OTH) AF: 0.308 AC: 649 AN: 2110

Alfa AF: 0.213 Hom.: 20471

Bravo AF: 0.371

Asia WGS AF: 0.390 AC: 1357 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.7
DANN	Benign	0.83
PhyloP100		0.31

Splicing

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

Other links and lift over

dbSNP: rs4723034; hg19: chr7-30994911;