NM_021081.6:c.124C>A

Variant names:

• chr20-37256458-G-T
• rs765871814
• NM_021081.6:c.124C>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_021081.6(GHRH):​c.124C>A​(p.Arg42Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: GHRH NM_021081.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.81
• Publications: 0 publications found

Genes affected

GHRH (HGNC:4265): (growth hormone releasing hormone) This gene encodes a member of the glucagon family of proteins. The encoded preproprotein is produced in the hypothalamus and cleaved to generate the mature factor, known as somatoliberin, which acts to stimulate growth hormone release from the pituitary gland. Variant receptors for somatoliberin have been found in several types of tumors, and antagonists of these receptors can inhibit the growth of the tumors. Defects in this gene are a cause of dwarfism, while hypersecretion of the encoded protein is a cause of gigantism. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed. [provided by RefSeq, Jan 2016]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP7: Synonymous conserved (PhyloP=1.81 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021081.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GHRH	NM_021081.6	MANE Select	c.124C>A	p.Arg42Arg	synonymous	Exon 3 of 5	NP_066567.1	P01286-1
	GHRH	NM_001184731.3		c.124C>A	p.Arg42Arg	synonymous	Exon 3 of 5	NP_001171660.1	P01286-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GHRH	ENST00000373614.7	TSL:1 MANE Select	c.124C>A	p.Arg42Arg	synonymous	Exon 3 of 5	ENSP00000362716.2	P01286-1
	GHRH	ENST00000237527.8	TSL:1	c.124C>A	p.Arg42Arg	synonymous	Exon 3 of 5	ENSP00000237527.4	P01286-2
	GHRH	ENST00000964612.1		c.124C>A	p.Arg42Arg	synonymous	Exon 3 of 5	ENSP00000634671.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	12
DANN	Uncertain	0.97
PhyloP100		1.8

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: rs765871814; hg19: chr20-35884861;