rs3744287

Positions:

• chr17-63918558-A-G

Variant summary

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

The NM_000515.5(GH1):​c.11-52T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0137 in 1,611,770 control chromosomes in the GnomAD database, including 277 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. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.017 (36 hom., cov: 32)
  • Exomes 𝑓: 0.013 (241 hom.)
• Consequence: GH1 NM_000515.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.47

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: This place is a probable branch point but likely benign (scored 0 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0711 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GH1	NM_000515.5	c.11-52T>C		intron_variant		ENST00000323322.10	NP_000506.2
GH1	NM_022559.4	c.11-52T>C		intron_variant			NP_072053.1
GH1	NM_022560.4	c.11-52T>C		intron_variant			NP_072054.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GH1	ENST00000323322.10	c.11-52T>C		intron_variant		1	NM_000515.5	ENSP00000312673	P1

Frequencies

GnomAD3 genomes AF: 0.0169 AC: 2557 AN: 151412 Hom.: 36 Cov.: 32

Gnomad AFR AF: 0.0222

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0142

Gnomad ASJ AF: 0.0523

Gnomad EAS AF: 0.0774

Gnomad SAS AF: 0.0192

Gnomad FIN AF: 0.00200

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0100

Gnomad OTH AF: 0.0249

GnomAD3 exomes AF: 0.0184 AC: 4607 AN: 249758 Hom.: 87 AF XY: 0.0183 AC XY: 2477 AN XY: 135210

Gnomad AFR exome AF: 0.0222

Gnomad AMR exome AF: 0.0115

Gnomad ASJ exome AF: 0.0441

Gnomad EAS exome AF: 0.0812

Gnomad SAS exome AF: 0.0211

Gnomad FIN exome AF: 0.00125

Gnomad NFE exome AF: 0.0100

Gnomad OTH exome AF: 0.0211

GnomAD4 exome AF: 0.0134 AC: 19561 AN: 1460242 Hom.: 241 Cov.: 34 AF XY: 0.0135 AC XY: 9804 AN XY: 726428

Gnomad4 AFR exome AF: 0.0228

Gnomad4 AMR exome AF: 0.0120

Gnomad4 ASJ exome AF: 0.0433

Gnomad4 EAS exome AF: 0.0615

Gnomad4 SAS exome AF: 0.0223

Gnomad4 FIN exome AF: 0.00131

Gnomad4 NFE exome AF: 0.0104

Gnomad4 OTH exome AF: 0.0177

GnomAD4 genome AF: 0.0169 AC: 2562 AN: 151528 Hom.: 36 Cov.: 32 AF XY: 0.0176 AC XY: 1300 AN XY: 73992

Gnomad4 AFR AF: 0.0222

Gnomad4 AMR AF: 0.0142

Gnomad4 ASJ AF: 0.0523

Gnomad4 EAS AF: 0.0774

Gnomad4 SAS AF: 0.0194

Gnomad4 FIN AF: 0.00200

Gnomad4 NFE AF: 0.0100

Gnomad4 OTH AF: 0.0256

Alfa AF: 0.0162 Hom.: 7

Bravo AF: 0.0178

Asia WGS AF: 0.0320 AC: 112 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.24
BranchPoint Hunter		0.0

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: rs3744287; hg19: chr17-61995918;