chr17-63918735-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_000515.5(GH1):c.10+32T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000543 in 1,613,656 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00057 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00054 ( 2 hom. )

Consequence

GH1
NM_000515.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.222

Publications

1 publications found

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 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:

ENSG00000285947 (HGNC:):

ENSG00000285947 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.000565 (86/152192) while in subpopulation AMR AF = 0.000458 (7/15292). AF 95% confidence interval is 0.000293. There are 1 homozygotes in GnomAd4. There are 44 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 2 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
GH1	NM_000515.5 link	c.10+32T>C	intron_variant	Intron 1 of 4	ENST00000323322.10	NP_000506.2	P01241-1B1A4G6
GH1	NM_022559.4 link	c.10+32T>C	intron_variant	Intron 1 of 4		NP_072053.1	P01241-2B1A4G7
GH1	NM_022560.4 link	c.10+32T>C	intron_variant	Intron 1 of 3		NP_072054.1	P01241-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GH1	ENST00000323322.10 link	c.10+32T>C		intron_variant	Intron 1 of 4	1	NM_000515.5	ENSP00000312673.5		P01241-1
ENSG00000285947	ENST00000647774.1 link	c.287-229T>C		intron_variant	Intron 4 of 7			ENSP00000497443.1		A0A3B3ISS9

Frequencies

GnomAD3 genomes

AF:

0.000566

AC:

AN:

152074

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00952

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000412

Gnomad OTH

AF:

0.000955

GnomAD2 exomes

AF:

0.000812

AC:

204

AN:

251152

AF XY:

0.000877

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.0103

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.000423

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.000541

AC:

791

AN:

1461464

Hom.:

Cov.:

AF XY:

0.000594

AC XY:

432

AN XY:

727024

show subpopulations

African (AFR)

AF:

0.0000598

AC:

AN:

33462

American (AMR)

AF:

0.000246

AC:

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.0102

AC:

266

AN:

26132

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.000928

AC:

AN:

86246

European-Finnish (FIN)

AF:

0.0000562

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00142

AC:

AN:

5646

European-Non Finnish (NFE)

AF:

0.000308

AC:

342

AN:

1111792

Other (OTH)

AF:

0.00129

AC:

AN:

60356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

107

160

214

267

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.000565

AC:

AN:

152192

Hom.:

Cov.:

AF XY:

0.000591

AC XY:

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.000289

AC:

AN:

41534

American (AMR)

AF:

0.000458

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00952

AC:

AN:

3466

East Asian (EAS)

AF:

0.000193

AC:

AN:

5184

South Asian (SAS)

AF:

0.000415

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000412

AC:

AN:

67974

Other (OTH)

AF:

0.000945

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00158

Hom.:

Bravo

AF:

0.000616

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.69

(source)

DANN

Benign

0.21

PhyloP100

-0.22

PromoterAI

0.010

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over