17-63917417-T-C

Position:

chr17-63917417-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS1

The NM_000515.5(GH1):c.546A>G(p.Leu182=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000239 in 1,613,910 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00024 ( 1 hom. )

Consequence

GH1
NM_000515.5 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 0.653

Variant links:

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]

GH1 links:

LOC112268204 (HGNC:):

LOC112268204 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 17-63917417-T-C is Benign according to our data. Variant chr17-63917417-T-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 703573.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}. Variant chr17-63917417-T-C is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0.653 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000197 (30/152248) while in subpopulation SAS AF= 0.000622 (3/4820). AF 95% confidence interval is 0.00017. There are 0 homozygotes in gnomad4. There are 15 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
GH1	NM_000515.5 linkuse as main transcript	c.546A>G	p.Leu182=	synonymous_variant	5/5	ENST00000323322.10
LOC112268204	XR_002958148.2 linkuse as main transcript	n.341-180T>C		intron_variant, non_coding_transcript_variant
GH1	NM_022559.4 linkuse as main transcript	c.501A>G	p.Leu167=	synonymous_variant	5/5
GH1	NM_022560.4 linkuse as main transcript	c.426A>G	p.Leu142=	synonymous_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GH1	ENST00000323322.10 linkuse as main transcript	c.546A>G	p.Leu182=	synonymous_variant	5/5	1	NM_000515.5	P1	P01241-1

Frequencies

GnomAD3 genomes

AF:

0.000197

AC:

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000221

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000207

AC:

AN:

251178

Hom.:

AF XY:

0.000221

AC XY:

AN XY:

135738

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000326

Gnomad SAS exome

AF:

0.000686

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000132

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000244

AC:

356

AN:

1461662

Hom.:

Cov.:

AF XY:

0.000287

AC XY:

209

AN XY:

727142

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.000201

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.000777

Gnomad4 FIN exome

AF:

0.0000936

Gnomad4 NFE exome

AF:

0.000219

Gnomad4 OTH exome

AF:

0.000282

GnomAD4 genome

AF:

0.000197

AC:

AN:

152248

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.000221

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000147

Hom.:

Bravo

AF:

0.000208

EpiCase

AF:

0.000164

EpiControl

AF:

0.000178

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Decreased response to growth hormone stimulation test

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Mar 27, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

5.9

DANN

Benign

0.68

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over