chr20-37259124-T-C

Variant names:

• chr20-37259124-T-C
• rs6032470
• NM_021081.6:c.-19-2216A>G

Variant summary

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

The NM_021081.6(GHRH):​c.-19-2216A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 152,144 control chromosomes in the GnomAD database, including 6,238 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 0.24 (6238 hom., cov: 32)
• Consequence: GHRH NM_021081.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.391
• Publications: 14 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.479 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GHRH	NM_021081.6	c.-19-2216A>G		intron_variant	Intron 1 of 4	ENST00000373614.7	NP_066567.1
GHRH	NM_001184731.3	c.-19-2216A>G		intron_variant	Intron 1 of 4		NP_001171660.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GHRH	ENST00000373614.7	c.-19-2216A>G		intron_variant	Intron 1 of 4	1	NM_021081.6	ENSP00000362716.2
GHRH	ENST00000237527.8	c.-19-2216A>G		intron_variant	Intron 1 of 4	1		ENSP00000237527.4

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36305 AN: 152026 Hom.: 6219 Cov.: 32

Gnomad AFR AF: 0.484

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.238

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.215

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

GnomAD4 genome AF: 0.239 AC: 36376 AN: 152144 Hom.: 6238 Cov.: 32 AF XY: 0.238 AC XY: 17690 AN XY: 74394

African (AFR) AF: 0.485 AC: 20091 AN: 41466

American (AMR) AF: 0.144 AC: 2208 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.178 AC: 618 AN: 3470

East Asian (EAS) AF: 0.238 AC: 1236 AN: 5184

South Asian (SAS) AF: 0.128 AC: 615 AN: 4820

European-Finnish (FIN) AF: 0.177 AC: 1875 AN: 10602

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.134 AC: 9104 AN: 68006

Other (OTH) AF: 0.217 AC: 458 AN: 2110

Alfa AF: 0.162 Hom.: 7447

Bravo AF: 0.247

Asia WGS AF: 0.237 AC: 826 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.3
DANN	Benign	0.35
PhyloP100		-0.39
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6032470; hg19: chr20-35887527;