7-30970345-C-T

Variant names:

• chr7-30970345-C-T
• rs10278927
• NM_000823.4:c.366+381C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000823.4(GHRHR):​c.366+381C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0725 in 152,150 control chromosomes in the GnomAD database, including 553 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.072 (553 hom., cov: 32)
• Consequence: GHRHR NM_000823.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0500
• Publications: 3 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.131 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.366+381C>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.366+381C>T		intron	N/A	ENSP00000320180.2
	GHRHR	ENST00000409904.7	TSL:1	c.174+381C>T		intron	N/A	ENSP00000387113.3
	GHRHR	ENST00000409316.5	TSL:1	c.-182+381C>T		intron	N/A	ENSP00000386602.1

Frequencies

GnomAD3 genomes AF: 0.0725 AC: 11016 AN: 152032 Hom.: 554 Cov.: 32

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.0639

Gnomad AMR AF: 0.0479

Gnomad ASJ AF: 0.0640

Gnomad EAS AF: 0.0639

Gnomad SAS AF: 0.0311

Gnomad FIN AF: 0.0160

Gnomad MID AF: 0.0924

Gnomad NFE AF: 0.0534

Gnomad OTH AF: 0.0737

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

GnomAD4 genome AF: 0.0725 AC: 11026 AN: 152150 Hom.: 553 Cov.: 32 AF XY: 0.0692 AC XY: 5146 AN XY: 74390

African (AFR) AF: 0.134 AC: 5556 AN: 41482

American (AMR) AF: 0.0479 AC: 732 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0640 AC: 222 AN: 3468

East Asian (EAS) AF: 0.0641 AC: 331 AN: 5164

South Asian (SAS) AF: 0.0311 AC: 150 AN: 4818

European-Finnish (FIN) AF: 0.0160 AC: 170 AN: 10616

Middle Eastern (MID) AF: 0.0925 AC: 27 AN: 292

European-Non Finnish (NFE) AF: 0.0533 AC: 3626 AN: 67996

Other (OTH) AF: 0.0729 AC: 154 AN: 2112

Alfa AF: 0.0531 Hom.: 362

Bravo AF: 0.0787

Asia WGS AF: 0.0500 AC: 177 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.8
DANN	Benign	0.74
PhyloP100		-0.050
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: rs10278927; hg19: chr7-31009960;