rs2267721

chr7-30965828-C-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
GHRHR	NM_000823.4	c.57+1703C>G		intron_variant		ENST00000326139.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GHRHR	ENST00000326139.7	c.57+1703C>G		intron_variant		1	NM_000823.4	P1
GHRHR	ENST00000466427.1	n.285-3006C>G		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.772

Gnomad4 AMR AF: 0.319

Gnomad4 ASJ AF: 0.293

Gnomad4 EAS AF: 0.285

Gnomad4 SAS AF: 0.448

Gnomad4 FIN AF: 0.280

Gnomad4 NFE AF: 0.342

Gnomad4 OTH AF: 0.425

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs2267721; hg19: chr7-31005443;