17-63917670-A-T

Position:

• chr17-63917670-A-T

Variant summary

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

The NM_000515.5(GH1):​c.456+90T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 1,613,692 control chromosomes in the GnomAD database, including 125,177 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (9221 hom., cov: 32)
  • Exomes 𝑓: 0.39 (115956 hom.)
• Consequence: GH1 NM_000515.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.02

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]

ENSG00000285947 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 17-63917670-A-T is Benign according to our data. Variant chr17-63917670-A-T is described in ClinVar as [Benign]. Clinvar id is 1293215.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GH1	NM_000515.5	c.456+90T>A		intron_variant		ENST00000323322.10	NP_000506.2
GH1	NM_022559.4	c.411+90T>A		intron_variant			NP_072053.1
GH1	NM_022560.4	c.336+90T>A		intron_variant			NP_072054.1
LOC112268204	XR_002958148.2	n.388+26A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GH1	ENST00000323322.10	c.456+90T>A		intron_variant		1	NM_000515.5	ENSP00000312673.5
ENSG00000285947	ENST00000647774.1	c.732+90T>A		intron_variant				ENSP00000497443.1

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48984 AN: 151980 Hom.: 9216 Cov.: 32

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.525

Gnomad AMR AF: 0.353

Gnomad ASJ AF: 0.440

Gnomad EAS AF: 0.410

Gnomad SAS AF: 0.267

Gnomad FIN AF: 0.409

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.415

Gnomad OTH AF: 0.355

GnomAD4 exome AF: 0.394 AC: 575572 AN: 1461594 Hom.: 115956 Cov.: 64 AF XY: 0.392 AC XY: 284997 AN XY: 727118

Gnomad4 AFR exome AF: 0.103

Gnomad4 AMR exome AF: 0.368

Gnomad4 ASJ exome AF: 0.454

Gnomad4 EAS exome AF: 0.413

Gnomad4 SAS exome AF: 0.281

Gnomad4 FIN exome AF: 0.399

Gnomad4 NFE exome AF: 0.410

Gnomad4 OTH exome AF: 0.391

GnomAD4 genome AF: 0.322 AC: 49007 AN: 152098 Hom.: 9221 Cov.: 32 AF XY: 0.321 AC XY: 23881 AN XY: 74358

Gnomad4 AFR AF: 0.115

Gnomad4 AMR AF: 0.353

Gnomad4 ASJ AF: 0.440

Gnomad4 EAS AF: 0.410

Gnomad4 SAS AF: 0.269

Gnomad4 FIN AF: 0.409

Gnomad4 NFE AF: 0.415

Gnomad4 OTH AF: 0.358

Alfa AF: 0.249 Hom.: 662

Bravo AF: 0.314

ClinVar

Significance: Benign

Submissions summary: Benign:2

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: 20650818, 10720078, 11904318) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.60
DANN	Benign	0.90

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: rs2665802; hg19: chr17-61995030; COSMIC: COSV60110519;