rs2267721

Variant names:

• chr7-30965828-C-G
• rs2267721
• NM_000823.4:c.57+1703C>G

Variant summary

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

The NM_000823.4(GHRHR):​c.57+1703C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 151,958 control chromosomes in the GnomAD database, including 18,575 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 0.45 (18575 hom., cov: 33)
• Consequence: GHRHR NM_000823.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.786
• 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: 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.765 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GHRHR	NM_000823.4	c.57+1703C>G		intron_variant	Intron 1 of 12	ENST00000326139.7	NP_000814.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GHRHR	ENST00000326139.7	c.57+1703C>G		intron_variant	Intron 1 of 12	1	NM_000823.4	ENSP00000320180.2
GHRHR	ENST00000466427.1	n.285-3006C>G		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes AF: 0.454 AC: 68862 AN: 151840 Hom.: 18543 Cov.: 33

Gnomad AFR AF: 0.772

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.286

Gnomad SAS AF: 0.450

Gnomad FIN AF: 0.280

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.341

Gnomad OTH AF: 0.425

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

GnomAD4 genome AF: 0.454 AC: 68941 AN: 151958 Hom.: 18575 Cov.: 33 AF XY: 0.447 AC XY: 33234 AN XY: 74270

African (AFR) AF: 0.772 AC: 31941 AN: 41396

American (AMR) AF: 0.319 AC: 4876 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 1018 AN: 3472

East Asian (EAS) AF: 0.285 AC: 1474 AN: 5170

South Asian (SAS) AF: 0.448 AC: 2157 AN: 4820

European-Finnish (FIN) AF: 0.280 AC: 2962 AN: 10574

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.342 AC: 23205 AN: 67944

Other (OTH) AF: 0.425 AC: 895 AN: 2108

Alfa AF: 0.396 Hom.: 1749

Bravo AF: 0.468

Asia WGS AF: 0.426 AC: 1482 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.3
DANN	Benign	0.80
PhyloP100		-0.79
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

Other links and lift over

dbSNP: rs2267721; hg19: chr7-31005443;