chr7-30974242-G-T

Position:

• chr7-30974242-G-T

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.751+104G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0419 in 1,319,858 control chromosomes in the GnomAD database, including 2,819 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.091 (1287 hom., cov: 32)
  • Exomes 𝑓: 0.036 (1532 hom.)
• Consequence: GHRHR NM_000823.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.525

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 7-30974242-G-T is Benign according to our data. Variant chr7-30974242-G-T is described in ClinVar as [Benign]. Clinvar id is 1262123.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GHRHR	NM_000823.4	c.751+104G>T		intron_variant		ENST00000326139.7	NP_000814.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GHRHR	ENST00000326139.7	c.751+104G>T		intron_variant		1	NM_000823.4	ENSP00000320180.2

Frequencies

GnomAD3 genomes AF: 0.0907 AC: 13799 AN: 152088 Hom.: 1283 Cov.: 32

Gnomad AFR AF: 0.238

Gnomad AMI AF: 0.0912

Gnomad AMR AF: 0.0476

Gnomad ASJ AF: 0.0470

Gnomad EAS AF: 0.0661

Gnomad SAS AF: 0.0576

Gnomad FIN AF: 0.0312

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0270

Gnomad OTH AF: 0.0773

GnomAD4 exome AF: 0.0355 AC: 41467 AN: 1167652 Hom.: 1532 Cov.: 16 AF XY: 0.0360 AC XY: 21311 AN XY: 591296

Gnomad4 AFR exome AF: 0.238

Gnomad4 AMR exome AF: 0.0328

Gnomad4 ASJ exome AF: 0.0382

Gnomad4 EAS exome AF: 0.0495

Gnomad4 SAS exome AF: 0.0617

Gnomad4 FIN exome AF: 0.0334

Gnomad4 NFE exome AF: 0.0252

Gnomad4 OTH exome AF: 0.0492

GnomAD4 genome AF: 0.0908 AC: 13816 AN: 152206 Hom.: 1287 Cov.: 32 AF XY: 0.0900 AC XY: 6697 AN XY: 74418

Gnomad4 AFR AF: 0.238

Gnomad4 AMR AF: 0.0476

Gnomad4 ASJ AF: 0.0470

Gnomad4 EAS AF: 0.0663

Gnomad4 SAS AF: 0.0570

Gnomad4 FIN AF: 0.0312

Gnomad4 NFE AF: 0.0270

Gnomad4 OTH AF: 0.0764

Alfa AF: 0.0101 Hom.: 5

Bravo AF: 0.0999

Asia WGS AF: 0.0700 AC: 243 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

Jun 20, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.8
DANN	Benign	0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs2074780; hg19: chr7-31013857; COSMIC: COSV58195960; COSMIC: COSV58195960;