rs2741

Variant names:

• chr7-30975950-T-G
• rs2741
• NM_000823.4:c.974+82T>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000823.4(GHRHR):​c.974+82T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 818,968 control chromosomes in the GnomAD database, including 5,654 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (922 hom., cov: 32)
  • Exomes 𝑓: 0.11 (4732 hom.)
• Consequence: GHRHR NM_000823.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.609
• Publications: 18 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 7-30975950-T-G is Benign according to our data. Variant chr7-30975950-T-G is described in ClinVar as Benign. ClinVar VariationId is 1221455.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GHRHR	NM_000823.4	c.974+82T>G		intron_variant	Intron 10 of 12	ENST00000326139.7	NP_000814.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GHRHR	ENST00000326139.7	c.974+82T>G		intron_variant	Intron 10 of 12	1	NM_000823.4	ENSP00000320180.2

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16122 AN: 152058 Hom.: 927 Cov.: 32

Gnomad AFR AF: 0.0894

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.0797

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.128

GnomAD4 exome AF: 0.114 AC: 76299 AN: 666792 Hom.: 4732 Cov.: 8 AF XY: 0.115 AC XY: 41502 AN XY: 359586

African (AFR) AF: 0.0904 AC: 1662 AN: 18380

American (AMR) AF: 0.135 AC: 5582 AN: 41278

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 3454 AN: 21016

East Asian (EAS) AF: 0.212 AC: 7584 AN: 35796

South Asian (SAS) AF: 0.133 AC: 9164 AN: 68854

European-Finnish (FIN) AF: 0.0804 AC: 4203 AN: 52268

Middle Eastern (MID) AF: 0.188 AC: 801 AN: 4252

European-Non Finnish (NFE) AF: 0.102 AC: 39849 AN: 390660

Other (OTH) AF: 0.117 AC: 4000 AN: 34288

GnomAD4 genome AF: 0.106 AC: 16108 AN: 152176 Hom.: 922 Cov.: 32 AF XY: 0.105 AC XY: 7806 AN XY: 74396

African (AFR) AF: 0.0893 AC: 3708 AN: 41502

American (AMR) AF: 0.126 AC: 1921 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.165 AC: 571 AN: 3470

East Asian (EAS) AF: 0.186 AC: 960 AN: 5154

South Asian (SAS) AF: 0.142 AC: 685 AN: 4828

European-Finnish (FIN) AF: 0.0797 AC: 845 AN: 10600

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.103 AC: 6983 AN: 68010

Other (OTH) AF: 0.128 AC: 270 AN: 2112

Alfa AF: 0.107 Hom.: 1432

Bravo AF: 0.111

Asia WGS AF: 0.149 AC: 518 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.3
DANN	Benign	0.73
PhyloP100		0.61
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2741; hg19: chr7-31015565; COSMIC: COSV58195915; COSMIC: COSV58195915;