rs9282698

chr17-63918735-A-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS1

The NM_000515.5(GH1):c.10+32T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000543 in 1,613,656 control chromosomes in the GnomAD database, including 3 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 0.00057 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00054 (2 hom.)
• Consequence: GH1 NM_000515.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.222

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000565 (86/152192) while in subpopulation AMR AF= 0.000458 (7/15292). AF 95% confidence interval is 0.000293. There are 1 homozygotes in gnomad4. There are 44 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GH1	NM_000515.5	c.10+32T>C		intron_variant		ENST00000323322.10
GH1	NM_022559.4	c.10+32T>C		intron_variant
GH1	NM_022560.4	c.10+32T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GH1	ENST00000323322.10	c.10+32T>C		intron_variant		1	NM_000515.5	P1

Frequencies

GnomAD3 genomes AF: 0.000566 AC: 86 AN: 152074 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000290

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00952

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.000955

GnomAD3 exomes AF: 0.000812 AC: 204 AN: 251152 Hom.: 1 AF XY: 0.000877 AC XY: 119 AN XY: 135730

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.0103

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.00105

Gnomad FIN exome AF: 0.0000924

Gnomad NFE exome AF: 0.000423

Gnomad OTH exome AF: 0.00131

GnomAD4 exome AF: 0.000541 AC: 791 AN: 1461464 Hom.: 2 Cov.: 35 AF XY: 0.000594 AC XY: 432 AN XY: 727024

Gnomad4 AFR exome AF: 0.0000598

Gnomad4 AMR exome AF: 0.000246

Gnomad4 ASJ exome AF: 0.0102

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000928

Gnomad4 FIN exome AF: 0.0000562

Gnomad4 NFE exome AF: 0.000308

Gnomad4 OTH exome AF: 0.00129

GnomAD4 genome AF: 0.000565 AC: 86 AN: 152192 Hom.: 1 Cov.: 32 AF XY: 0.000591 AC XY: 44 AN XY: 74422

Gnomad4 AFR AF: 0.000289

Gnomad4 AMR AF: 0.000458

Gnomad4 ASJ AF: 0.00952

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000412

Gnomad4 OTH AF: 0.000945

Alfa AF: 0.00158 Hom.: 0

Bravo AF: 0.000616

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.69
Dann	Benign	0.21

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: rs9282698; hg19: chr17-61996095;