chr7-30984558-T-C

Variant names:

• chr7-30984558-T-C
• rs11771444
• ENST00000461424.5:n.922+199T>C

Variant summary

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

The ENST00000461424.5(GHRHR):​n.922+199T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 151,872 control chromosomes in the GnomAD database, including 16,805 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 0.39 (16805 hom., cov: 31)
• Consequence: GHRHR ENST00000461424.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.116
• Publications: 1 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.801 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105375222	XR_001745155.2	n.536+199T>C		intron_variant	Intron 1 of 2
LOC105375222	XR_001745156.2	n.536+199T>C		intron_variant	Intron 1 of 3
LOC105375222	XR_927159.2	n.536+199T>C		intron_variant	Intron 1 of 3
LOC105375222	XR_927160.2	n.536+199T>C		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GHRHR	ENST00000461424.5	n.922+199T>C		intron_variant	Intron 8 of 8	2
GHRHR	ENST00000473133.1	n.279+199T>C		intron_variant	Intron 1 of 1	3
GHRHR	ENST00000611037.1	c.*367T>C		downstream_gene_variant		5		ENSP00000480159.1

Frequencies

GnomAD3 genomes AF: 0.389 AC: 59002 AN: 151754 Hom.: 16778 Cov.: 31

Gnomad AFR AF: 0.808

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.339

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.364

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

GnomAD4 genome AF: 0.389 AC: 59066 AN: 151872 Hom.: 16805 Cov.: 31 AF XY: 0.382 AC XY: 28318 AN XY: 74224

African (AFR) AF: 0.808 AC: 33502 AN: 41454

American (AMR) AF: 0.243 AC: 3705 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.339 AC: 1174 AN: 3468

East Asian (EAS) AF: 0.159 AC: 820 AN: 5150

South Asian (SAS) AF: 0.336 AC: 1606 AN: 4784

European-Finnish (FIN) AF: 0.149 AC: 1569 AN: 10546

Middle Eastern (MID) AF: 0.479 AC: 140 AN: 292

European-Non Finnish (NFE) AF: 0.228 AC: 15501 AN: 67920

Other (OTH) AF: 0.364 AC: 766 AN: 2104

Alfa AF: 0.246 Hom.: 2421

Bravo AF: 0.412

Asia WGS AF: 0.300 AC: 1044 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.4
DANN	Benign	0.38
PhyloP100		0.12

Splicing

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

Other links and lift over

dbSNP: rs11771444; hg19: chr7-31024173;