7-30964346-A-G

Position:

• chr7-30964346-A-G

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.57+221A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0754 in 152,142 control chromosomes in the GnomAD database, including 558 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.075 (558 hom., cov: 33)
• Consequence: GHRHR NM_000823.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.990

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=-0.9).
• BP6: Variant 7-30964346-A-G is Benign according to our data. Variant chr7-30964346-A-G is described in ClinVar as [Benign]. Clinvar id is 1281216.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GHRHR	NM_000823.4	c.57+221A>G		intron_variant		ENST00000326139.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GHRHR	ENST00000326139.7	c.57+221A>G		intron_variant		1	NM_000823.4	P1
GHRHR	ENST00000466427.1	n.285-4488A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0755 AC: 11473 AN: 152024 Hom.: 558 Cov.: 33

Gnomad AFR AF: 0.0483

Gnomad AMI AF: 0.0936

Gnomad AMR AF: 0.0944

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.0556

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.0493

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.0785

Gnomad OTH AF: 0.114

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

GnomAD4 genome AF: 0.0754 AC: 11474 AN: 152142 Hom.: 558 Cov.: 33 AF XY: 0.0764 AC XY: 5682 AN XY: 74376

Gnomad4 AFR AF: 0.0482

Gnomad4 AMR AF: 0.0943

Gnomad4 ASJ AF: 0.215

Gnomad4 EAS AF: 0.0557

Gnomad4 SAS AF: 0.156

Gnomad4 FIN AF: 0.0493

Gnomad4 NFE AF: 0.0785

Gnomad4 OTH AF: 0.114

Alfa AF: 0.0793 Hom.: 136

Bravo AF: 0.0761

Asia WGS AF: 0.0880 AC: 304 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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.43
DANN	Benign	0.56

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: rs33944945; hg19: chr7-31003961;