chr7-30989018-A-G

Variant names:

• chr7-30989018-A-G
• rs11760522
• ENST00000473133.1:n.280-4155A>G

Variant summary

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

The ENST00000473133.1(GHRHR):​n.280-4155A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 152,104 control chromosomes in the GnomAD database, including 13,422 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 0.36 (13422 hom., cov: 32)
• Consequence: GHRHR ENST00000473133.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.01
• 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)

LOC105375222 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.701 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105375222	XR_001745155.2	n.537-4155A>G		intron_variant	Intron 1 of 2
LOC105375222	XR_001745156.2	n.537-4155A>G		intron_variant	Intron 1 of 3
LOC105375222	XR_927159.2	n.537-4155A>G		intron_variant	Intron 1 of 3
LOC105375222	XR_927160.2	n.537-4155A>G		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GHRHR	ENST00000473133.1	n.280-4155A>G		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.357 AC: 54186 AN: 151986 Hom.: 13400 Cov.: 32

Gnomad AFR AF: 0.708

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.333

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

GnomAD4 genome AF: 0.357 AC: 54245 AN: 152104 Hom.: 13422 Cov.: 32 AF XY: 0.350 AC XY: 26045 AN XY: 74360

African (AFR) AF: 0.708 AC: 29369 AN: 41468

American (AMR) AF: 0.224 AC: 3433 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.313 AC: 1087 AN: 3472

East Asian (EAS) AF: 0.140 AC: 722 AN: 5140

South Asian (SAS) AF: 0.340 AC: 1636 AN: 4814

European-Finnish (FIN) AF: 0.148 AC: 1574 AN: 10608

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.226 AC: 15336 AN: 67986

Other (OTH) AF: 0.334 AC: 704 AN: 2110

Alfa AF: 0.273 Hom.: 2536

Bravo AF: 0.375

Asia WGS AF: 0.284 AC: 990 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.82
DANN	Benign	0.48
PhyloP100		-3.0

Splicing

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

Other links and lift over

dbSNP: rs11760522; hg19: chr7-31028633;