rs2267723

Variant names:

• chr7-30967327-A-G
• rs2267723
• NM_000823.4:c.58-1507A>G

Your query was ambiguous. Multiple possible variants found:

• chr7-30967327-A-G
• chr7-30967327-A-T

Variant summary

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

The NM_000823.4(GHRHR):​c.58-1507A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 152,046 control chromosomes in the GnomAD database, including 24,791 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 0.54 (24791 hom., cov: 32)
• Consequence: GHRHR NM_000823.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0860
• Publications: 13 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.816 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GHRHR	NM_000823.4	c.58-1507A>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.58-1507A>G		intron_variant	Intron 1 of 12	1	NM_000823.4	ENSP00000320180.2
GHRHR	ENST00000466427.1	n.285-1507A>G		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes AF: 0.542 AC: 82333 AN: 151928 Hom.: 24752 Cov.: 32

Gnomad AFR AF: 0.823

Gnomad AMI AF: 0.501

Gnomad AMR AF: 0.418

Gnomad ASJ AF: 0.453

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.509

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.507

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

GnomAD4 genome AF: 0.542 AC: 82423 AN: 152046 Hom.: 24791 Cov.: 32 AF XY: 0.537 AC XY: 39926 AN XY: 74288

African (AFR) AF: 0.823 AC: 34147 AN: 41492

American (AMR) AF: 0.418 AC: 6386 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.453 AC: 1571 AN: 3468

East Asian (EAS) AF: 0.256 AC: 1322 AN: 5170

South Asian (SAS) AF: 0.509 AC: 2447 AN: 4810

European-Finnish (FIN) AF: 0.429 AC: 4526 AN: 10550

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.446 AC: 30320 AN: 67964

Other (OTH) AF: 0.508 AC: 1070 AN: 2106

Alfa AF: 0.476 Hom.: 30382

Bravo AF: 0.555

Asia WGS AF: 0.423 AC: 1470 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.4
DANN	Benign	0.70
PhyloP100		-0.086
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: rs2267723; hg19: chr7-31006942;