rs2001344

Positions:

• chr17-63918647-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000515.5(GH1):​c.10+120G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00886 in 1,609,934 control chromosomes in the GnomAD database, including 1,003 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 0.046 (533 hom., cov: 32)
  • Exomes 𝑓: 0.0049 (470 hom.)
• Consequence: GH1 NM_000515.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.234

Genes affected

GH1 (HGNC:4261): (growth hormone 1) The protein encoded by this gene is a member of the somatotropin/prolactin family of hormones which play an important role in growth control. The gene, along with four other related genes, is located at the growth hormone locus on chromosome 17 where they are interspersed in the same transcriptional orientation; an arrangement which is thought to have evolved by a series of gene duplications. The five genes share a remarkably high degree of sequence identity. Alternative splicing generates additional isoforms of each of the five growth hormones, leading to further diversity and potential for specialization. This particular family member is expressed in the pituitary but not in placental tissue as is the case for the other four genes in the growth hormone locus. Mutations in or deletions of the gene lead to growth hormone deficiency and short stature. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -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 = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GH1	NM_000515.5	c.10+120G>C		intron_variant		ENST00000323322.10
GH1	NM_022559.4	c.10+120G>C		intron_variant
GH1	NM_022560.4	c.10+120G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GH1	ENST00000323322.10	c.10+120G>C		intron_variant		1	NM_000515.5	P1

Frequencies

GnomAD3 genomes AF: 0.0464 AC: 7058 AN: 152166 Hom.: 533 Cov.: 32

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0190

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000911

Gnomad OTH AF: 0.0325

GnomAD4 exome AF: 0.00493 AC: 7186 AN: 1457650 Hom.: 470 Cov.: 34 AF XY: 0.00426 AC XY: 3091 AN XY: 725238

Gnomad4 AFR exome AF: 0.165

Gnomad4 AMR exome AF: 0.00887

Gnomad4 ASJ exome AF: 0.000766

Gnomad4 EAS exome AF: 0.00144

Gnomad4 SAS exome AF: 0.000743

Gnomad4 FIN exome AF: 0.0000375

Gnomad4 NFE exome AF: 0.000445

Gnomad4 OTH exome AF: 0.0106

GnomAD4 genome AF: 0.0465 AC: 7076 AN: 152284 Hom.: 533 Cov.: 32 AF XY: 0.0448 AC XY: 3333 AN XY: 74478

Gnomad4 AFR AF: 0.160

Gnomad4 AMR AF: 0.0190

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00154

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000911

Gnomad4 OTH AF: 0.0322

Alfa AF: 0.0362 Hom.: 36

Bravo AF: 0.0537

Asia WGS AF: 0.0110 AC: 39 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	2.2
DANN	Benign	0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2001344; hg19: chr17-61996007;