rs10265249

chr7-30945961-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000466427.1(GHRHR):n.284+7009G>A variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0756 in 151,848 control chromosomes in the GnomAD database, including 629 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 0.076 (629 hom., cov: 32)
• Consequence: GHRHR ENST00000466427.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36

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 = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GHRHR	ENST00000466427.1	n.284+7009G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0755 AC: 11454 AN: 151730 Hom.: 627 Cov.: 32

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.0510

Gnomad ASJ AF: 0.0312

Gnomad EAS AF: 0.00232

Gnomad SAS AF: 0.0162

Gnomad FIN AF: 0.0293

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0499

Gnomad OTH AF: 0.0708

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

GnomAD4 genome AF: 0.0756 AC: 11475 AN: 151848 Hom.: 629 Cov.: 32 AF XY: 0.0735 AC XY: 5454 AN XY: 74214

Gnomad4 AFR AF: 0.160

Gnomad4 AMR AF: 0.0509

Gnomad4 ASJ AF: 0.0312

Gnomad4 EAS AF: 0.00271

Gnomad4 SAS AF: 0.0165

Gnomad4 FIN AF: 0.0293

Gnomad4 NFE AF: 0.0499

Gnomad4 OTH AF: 0.0696

Alfa AF: 0.0553 Hom.: 434

Bravo AF: 0.0821

Asia WGS AF: 0.0230 AC: 84 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	2.2
Dann	Benign	0.84

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10265249; hg19: chr7-30985576;