chr7-30974242-G-T

Variant names:

• chr7-30974242-G-T
• rs2074780
• NM_000823.4:c.751+104G>T

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.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
• 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)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000823.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GHRHR	NM_000823.4	MANE Select	c.751+104G>T		intron	N/A	NP_000814.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GHRHR	ENST00000326139.7	TSL:1 MANE Select	c.751+104G>T		intron	N/A	ENSP00000320180.2
	GHRHR	ENST00000409904.7	TSL:1	c.559+104G>T		intron	N/A	ENSP00000387113.3
	GHRHR	ENST00000409316.5	TSL:1	c.51-187G>T		intron	N/A	ENSP00000386602.1

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

African (AFR) AF: 0.238 AC: 6502 AN: 27340

American (AMR) AF: 0.0328 AC: 1401 AN: 42726

Ashkenazi Jewish (ASJ) AF: 0.0382 AC: 892 AN: 23326

East Asian (EAS) AF: 0.0495 AC: 1889 AN: 38178

South Asian (SAS) AF: 0.0617 AC: 4814 AN: 78050

European-Finnish (FIN) AF: 0.0334 AC: 1606 AN: 48050

Middle Eastern (MID) AF: 0.0816 AC: 354 AN: 4338

European-Non Finnish (NFE) AF: 0.0252 AC: 21535 AN: 855326

Other (OTH) AF: 0.0492 AC: 2474 AN: 50318

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

African (AFR) AF: 0.238 AC: 9864 AN: 41496

American (AMR) AF: 0.0476 AC: 728 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0470 AC: 163 AN: 3470

East Asian (EAS) AF: 0.0663 AC: 343 AN: 5174

South Asian (SAS) AF: 0.0570 AC: 275 AN: 4822

European-Finnish (FIN) AF: 0.0312 AC: 332 AN: 10626

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.0270 AC: 1834 AN: 67998

Other (OTH) AF: 0.0764 AC: 161 AN: 2106

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

Jun 20, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.8
DANN	Benign	0.34
PhyloP100		0.53
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: rs2074780; hg19: chr7-31013857; COSMIC: COSV58195960; COSMIC: COSV58195960;