chr17-63918844-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.35

Publications

14 publications found

Variant links:

COSMIC-nc: COSV105177127

Genes affected

ENSG00000285947 (HGNC:):

ENSG00000285947 links:

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

GH1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId 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	Effect	MANE	Protein
GH1	NM_000515.5 link	c.-68A>G	upstream_gene_variant	ENST00000323322.10	NP_000506.2
GH1	NM_022559.4 link	c.-68A>G	upstream_gene_variant		NP_072053.1
GH1	NM_022560.4 link	c.-68A>G	upstream_gene_variant		NP_072054.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000285947	ENST00000647774.1 link	c.287-338A>G		intron_variant	Intron 4 of 7			ENSP00000497443.1
GH1	ENST00000323322.10 link	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.:

show subpopulations

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.:

AF XY:

0.405

AC XY:

294324

AN XY:

725914

show subpopulations

African (AFR)

AF:

0.429

AC:

14188

AN:

33076

American (AMR)

AF:

0.270

AC:

12071

AN:

44634

Ashkenazi Jewish (ASJ)

AF:

0.472

AC:

12328

AN:

26120

East Asian (EAS)

AF:

0.293

AC:

11645

AN:

39684

South Asian (SAS)

AF:

0.297

AC:

25608

AN:

86182

European-Finnish (FIN)

AF:

0.356

AC:

18988

AN:

53398

Middle Eastern (MID)

AF:

0.425

AC:

2447

AN:

5754

European-Non Finnish (NFE)

AF:

0.426

AC:

473384

AN:

1110034

Other (OTH)

AF:

0.408

AC:

24599

AN:

60270

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

17746

35492

53238

70984

88730

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14246

28492

42738

56984

71230

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.408

AC:

61619

AN:

150962

Hom.:

12912

Cov.:

AF XY:

0.399

AC XY:

29473

AN XY:

73802

show subpopulations

African (AFR)

AF:

0.431

AC:

17510

AN:

40630

American (AMR)

AF:

0.327

AC:

4974

AN:

15218

Ashkenazi Jewish (ASJ)

AF:

0.469

AC:

1625

AN:

3468

East Asian (EAS)

AF:

0.306

AC:

1581

AN:

5172

South Asian (SAS)

AF:

0.276

AC:

1319

AN:

4778

European-Finnish (FIN)

AF:

0.359

AC:

3802

AN:

10578

Middle Eastern (MID)

AF:

0.417

AC:

121

AN:

290

European-Non Finnish (NFE)

AF:

0.434

AC:

29423

AN:

67830

Other (OTH)

AF:

0.414

AC:

866

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

1811

3622

5434

7245

9056

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

580

1160

1740

2320

2900

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 12655556) -

Isolated congenital growth hormone deficiency

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.62

(source)

DANN

Benign

0.90

PhyloP100

-1.3

PromoterAI

-0.015

Neutral

(source)

Mutation Taster

=156/144

polymorphism

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over