chr7-30945961-G-A

Variant names:

• chr7-30945961-G-A
• rs10265249
• ENST00000466427.1:n.284+7009G>A

Variant summary

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

The ENST00000466427.1(GHRHR):​n.284+7009G>A variant causes a intron 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36
• 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 = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GHRHR	ENST00000466427.1	n.284+7009G>A		intron_variant	Intron 1 of 1	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

African (AFR) AF: 0.160 AC: 6635 AN: 41388

American (AMR) AF: 0.0509 AC: 776 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.0312 AC: 108 AN: 3464

East Asian (EAS) AF: 0.00271 AC: 14 AN: 5168

South Asian (SAS) AF: 0.0165 AC: 79 AN: 4798

European-Finnish (FIN) AF: 0.0293 AC: 309 AN: 10552

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0499 AC: 3387 AN: 67906

Other (OTH) AF: 0.0696 AC: 147 AN: 2112

Alfa AF: 0.0587 Hom.: 691

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
PhyloP100		-1.4

Splicing

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

Other links and lift over

dbSNP: rs10265249; hg19: chr7-30985576;