7-30977488-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000823.4(GHRHR):c.1146+166G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 152,070 control chromosomes in the GnomAD database, including 9,824 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.34 (9824 hom., cov: 32)
• Consequence: GHRHR NM_000823.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.239

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 7-30977488-G-C is Benign according to our data. Variant chr7-30977488-G-C is described in ClinVar as [Benign]. Clinvar id is 1259484.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GHRHR	NM_000823.4	c.1146+166G>C		intron_variant		ENST00000326139.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GHRHR	ENST00000326139.7	c.1146+166G>C		intron_variant		1	NM_000823.4	P1

Frequencies

GnomAD3 genomes AF: 0.341 AC: 51833 AN: 151950 Hom.: 9786 Cov.: 32

Gnomad AFR AF: 0.496

Gnomad AMI AF: 0.328

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.0350

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.268

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.296

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

GnomAD4 genome AF: 0.341 AC: 51926 AN: 152070 Hom.: 9824 Cov.: 32 AF XY: 0.337 AC XY: 25088 AN XY: 74350

Gnomad4 AFR AF: 0.497

Gnomad4 AMR AF: 0.247

Gnomad4 ASJ AF: 0.212

Gnomad4 EAS AF: 0.0349

Gnomad4 SAS AF: 0.300

Gnomad4 FIN AF: 0.303

Gnomad4 NFE AF: 0.309

Gnomad4 OTH AF: 0.298

Alfa AF: 0.172 Hom.: 322

Bravo AF: 0.339

Asia WGS AF: 0.214 AC: 746 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
Cadd	Benign	10
Dann	Benign	0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4988505; hg19: chr7-31017103; COSMIC: COSV58195931; COSMIC: COSV58195931;