NM_000823.4:c.366+381C>T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GHRHR	NM_000823.4	c.366+381C>T		intron_variant	Intron 4 of 12	ENST00000326139.7	NP_000814.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GHRHR	ENST00000326139.7	c.366+381C>T		intron_variant	Intron 4 of 12	1	NM_000823.4	ENSP00000320180.2

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

Gnomad4 AFR AF: 0.134

Gnomad4 AMR AF: 0.0479

Gnomad4 ASJ AF: 0.0640

Gnomad4 EAS AF: 0.0641

Gnomad4 SAS AF: 0.0311

Gnomad4 FIN AF: 0.0160

Gnomad4 NFE AF: 0.0533

Gnomad4 OTH AF: 0.0729

Alfa AF: 0.0499 Hom.: 264

Bravo AF: 0.0787

Asia WGS AF: 0.0500 AC: 177 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.8
DANN	Benign	0.74

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: rs10278927; hg19: chr7-31009960;