17-63918868-ACC-AC

Position:

• chr17-63918868-ACC-AC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The 17-63918868-AC-A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0951 in 1,609,300 control chromosomes in the GnomAD database, including 8,066 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.080 (622 hom., cov: 31)
  • Exomes 𝑓: 0.097 (7444 hom.)
• Consequence: GH1 NM_000515.5 upstream_gene
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.57

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 -10 ACMG points.

• BP6: Variant 17-63918868-AC-A is Benign according to our data. Variant chr17-63918868-AC-A is described in ClinVar as [Benign]. Clinvar id is 1248032.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GH1	NM_000515.5			upstream_gene_variant		ENST00000323322.10	NP_000506.2
GH1	NM_022559.4			upstream_gene_variant			NP_072053.1
GH1	NM_022560.4			upstream_gene_variant			NP_072054.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GH1	ENST00000323322.10			upstream_gene_variant		1	NM_000515.5	ENSP00000312673	P1
GH1	ENST00000342364.8			upstream_gene_variant		5		ENSP00000339278
GH1	ENST00000617086.1			upstream_gene_variant		5		ENSP00000481276

Frequencies

GnomAD3 genomes AF: 0.0803 AC: 12176 AN: 151596 Hom.: 622 Cov.: 31

Gnomad AFR AF: 0.0598

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.0547

Gnomad ASJ AF: 0.0847

Gnomad EAS AF: 0.00906

Gnomad SAS AF: 0.0431

Gnomad FIN AF: 0.0740

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.0750

GnomAD4 exome AF: 0.0966 AC: 140802 AN: 1457586 Hom.: 7444 Cov.: 33 AF XY: 0.0958 AC XY: 69473 AN XY: 725210

Gnomad4 AFR exome AF: 0.0613

Gnomad4 AMR exome AF: 0.0401

Gnomad4 ASJ exome AF: 0.0794

Gnomad4 EAS exome AF: 0.00953

Gnomad4 SAS exome AF: 0.0515

Gnomad4 FIN exome AF: 0.0777

Gnomad4 NFE exome AF: 0.109

Gnomad4 OTH exome AF: 0.0844

GnomAD4 genome AF: 0.0803 AC: 12181 AN: 151714 Hom.: 622 Cov.: 31 AF XY: 0.0772 AC XY: 5727 AN XY: 74202

Gnomad4 AFR AF: 0.0598

Gnomad4 AMR AF: 0.0546

Gnomad4 ASJ AF: 0.0847

Gnomad4 EAS AF: 0.00927

Gnomad4 SAS AF: 0.0430

Gnomad4 FIN AF: 0.0740

Gnomad4 NFE AF: 0.106

Gnomad4 OTH AF: 0.0742

Alfa AF: 0.0912 Hom.: 84

Bravo AF: 0.0777

Asia WGS AF: 0.0220 AC: 76 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11568827; hg19: chr17-61996228;