rs6171

Positions:

• chr17-63918844-T-C
• chr17-63918844-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000647774.1(ENSG00000285947):​c.287-338A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 1,610,114 control chromosomes in the GnomAD database, including 136,797 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.41 (12912 hom., cov: 32)
  • Exomes 𝑓: 0.41 (123885 hom.)
• Consequence: ENSG00000285947 ENST00000647774.1 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.35

Genes affected

ENSG00000285947 (HGNC:):

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 17-63918844-T-C is Benign according to our data. Variant chr17-63918844-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 369220.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.43 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.63918844T>C		intergenic_region
GH1	NM_000515.5	c.-68A>G		upstream_gene_variant		ENST00000323322.10	NP_000506.2
GH1	NM_022559.4	c.-68A>G		upstream_gene_variant			NP_072053.1
GH1	NM_022560.4	c.-68A>G		upstream_gene_variant			NP_072054.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000285947	ENST00000647774.1	c.287-338A>G		intron_variant				ENSP00000497443.1
GH1	ENST00000323322.10	c.-68A>G		upstream_gene_variant		1	NM_000515.5	ENSP00000312673.5

Frequencies

GnomAD3 genomes AF: 0.408 AC: 61570 AN: 150844 Hom.: 12901 Cov.: 32

Gnomad AFR AF: 0.431

Gnomad AMI AF: 0.439

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.469

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.417

Gnomad NFE AF: 0.434

Gnomad OTH AF: 0.411

GnomAD4 exome AF: 0.408 AC: 595258 AN: 1459152 Hom.: 123885 Cov.: 44 AF XY: 0.405 AC XY: 294324 AN XY: 725914

Gnomad4 AFR exome AF: 0.429

Gnomad4 AMR exome AF: 0.270

Gnomad4 ASJ exome AF: 0.472

Gnomad4 EAS exome AF: 0.293

Gnomad4 SAS exome AF: 0.297

Gnomad4 FIN exome AF: 0.356

Gnomad4 NFE exome AF: 0.426

Gnomad4 OTH exome AF: 0.408

GnomAD4 genome AF: 0.408 AC: 61619 AN: 150962 Hom.: 12912 Cov.: 32 AF XY: 0.399 AC XY: 29473 AN XY: 73802

Gnomad4 AFR AF: 0.431

Gnomad4 AMR AF: 0.327

Gnomad4 ASJ AF: 0.469

Gnomad4 EAS AF: 0.306

Gnomad4 SAS AF: 0.276

Gnomad4 FIN AF: 0.359

Gnomad4 NFE AF: 0.434

Gnomad4 OTH AF: 0.414

Alfa AF: 0.277 Hom.: 673

Bravo AF: 0.405

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	This variant is associated with the following publications: (PMID: 12655556) -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Isolated congenital growth hormone deficiency Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.62
DANN	Benign	0.90

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6171; hg19: chr17-61996204; COSMIC: COSV105177127;