chr17-63918868-AC-A

Variant names:

• chr17-63918868-AC-A
• rs11568827
• ENST00000647774.1:c.287-363delG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000647774.1(ENSG00000285947):​c.287-363delG variant causes a intron 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: ENSG00000285947 ENST00000647774.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.57
• Publications: 8 publications found

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]

GH1 Gene-Disease associations (from GenCC):

• isolated growth hormone deficiency type IA

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet
• isolated growth hormone deficiency type II

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet
• isolated growth hormone deficiency type IB

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• short stature due to growth hormone qualitative anomaly

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000647774.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GH1	NM_000515.5	MANE Select	c.-93delG		upstream_gene	N/A	NP_000506.2
	GH1	NM_022559.4		c.-93delG		upstream_gene	N/A	NP_072053.1
	GH1	NM_022560.4		c.-93delG		upstream_gene	N/A	NP_072054.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000285947	ENST00000647774.1		c.287-363delG		intron	N/A	ENSP00000497443.1
	GH1	ENST00000323322.10	TSL:1 MANE Select	c.-93delG		upstream_gene	N/A	ENSP00000312673.5
	GH1	ENST00000458650.6	TSL:1	c.-93delG		upstream_gene	N/A	ENSP00000408486.2

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

African (AFR) AF: 0.0613 AC: 2031 AN: 33108

American (AMR) AF: 0.0401 AC: 1782 AN: 44478

Ashkenazi Jewish (ASJ) AF: 0.0794 AC: 2067 AN: 26042

East Asian (EAS) AF: 0.00953 AC: 378 AN: 39666

South Asian (SAS) AF: 0.0515 AC: 4425 AN: 85942

European-Finnish (FIN) AF: 0.0777 AC: 4145 AN: 53344

Middle Eastern (MID) AF: 0.0931 AC: 536 AN: 5758

European-Non Finnish (NFE) AF: 0.109 AC: 120355 AN: 1109022

Other (OTH) AF: 0.0844 AC: 5083 AN: 60226

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

African (AFR) AF: 0.0598 AC: 2461 AN: 41120

American (AMR) AF: 0.0546 AC: 834 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0847 AC: 294 AN: 3470

East Asian (EAS) AF: 0.00927 AC: 48 AN: 5178

South Asian (SAS) AF: 0.0430 AC: 206 AN: 4794

European-Finnish (FIN) AF: 0.0740 AC: 784 AN: 10594

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.106 AC: 7224 AN: 67982

Other (OTH) AF: 0.0742 AC: 156 AN: 2102

Alfa AF: 0.0912 Hom.: 84

Bravo AF: 0.0777

Asia WGS AF: 0.0220 AC: 76 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.6
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs11568827; hg19: chr17-61996228;