ENST00000466427.1:n.285-5026C>T

Variant names:

• chr7-30963808-C-T
• rs2302019
• ENST00000466427.1:n.285-5026C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000466427.1(GHRHR):​n.285-5026C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.545 in 152,104 control chromosomes in the GnomAD database, including 26,039 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.55 (26039 hom., cov: 33)
• Consequence: GHRHR ENST00000466427.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.834
• Publications: 8 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 7-30963808-C-T is Benign according to our data. Variant chr7-30963808-C-T is described in ClinVar as Benign. ClinVar VariationId is 1258935.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.869 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
	GHRHR	NM_000823.4	MANE Select	c.-261C>T		upstream_gene	N/A	NP_000814.2	A0A090N8Y6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GHRHR	ENST00000466427.1	TSL:5	n.285-5026C>T		intron	N/A
	GHRHR	ENST00000326139.7	TSL:1 MANE Select	c.-261C>T		upstream_gene	N/A	ENSP00000320180.2	Q02643

Frequencies

GnomAD3 genomes AF: 0.545 AC: 82797 AN: 151986 Hom.: 25982 Cov.: 33

Gnomad AFR AF: 0.877

Gnomad AMI AF: 0.402

Gnomad AMR AF: 0.421

Gnomad ASJ AF: 0.511

Gnomad EAS AF: 0.336

Gnomad SAS AF: 0.606

Gnomad FIN AF: 0.332

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.418

Gnomad OTH AF: 0.547

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

GnomAD4 genome AF: 0.545 AC: 82904 AN: 152104 Hom.: 26039 Cov.: 33 AF XY: 0.540 AC XY: 40148 AN XY: 74332

African (AFR) AF: 0.877 AC: 36443 AN: 41558

American (AMR) AF: 0.420 AC: 6422 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.511 AC: 1772 AN: 3470

East Asian (EAS) AF: 0.335 AC: 1724 AN: 5140

South Asian (SAS) AF: 0.604 AC: 2907 AN: 4810

European-Finnish (FIN) AF: 0.332 AC: 3513 AN: 10584

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.418 AC: 28414 AN: 67952

Other (OTH) AF: 0.548 AC: 1156 AN: 2110

Alfa AF: 0.461 Hom.: 76885

Bravo AF: 0.561

Asia WGS AF: 0.519 AC: 1805 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	-0.87
CADD	Benign	0.72
DANN	Benign	0.34
PhyloP100		-0.83
PromoterAI		0.0068	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs2302019; hg19: chr7-31003423; COSMIC: COSV107358750;