Variant rs695 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000515.5(GH1):c.-63A>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0978 in 1,609,998 control chromosomes in the GnomAD database, including 8,410 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 952 hom., cov: 32)

Exomes 𝑓: 0.097 ( 7458 hom. )

Consequence

GH1
NM_000515.5 5_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.15

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 17-63918839-T-A is Benign according to our data. Variant chr17-63918839-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 369218.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
GH1	NM_000515.5 linkuse as main transcript	c.-63A>T	5_prime_UTR_variant	1/5	ENST00000323322.10
GH1	NM_022559.4 linkuse as main transcript	c.-63A>T	5_prime_UTR_variant	1/5
GH1	NM_022560.4 linkuse as main transcript	c.-63A>T	5_prime_UTR_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GH1	ENST00000323322.10 linkuse as main transcript	c.-63A>T		5_prime_UTR_variant	1/5	1	NM_000515.5	P1	P01241-1

Frequencies

GnomAD3 genomes

AF:

0.105

AC:

15912

AN:

150964

Hom.:

954

Cov.:

show subpopulations

Gnomad AFR

AF:

0.128

Gnomad AMI

AF:

0.146

Gnomad AMR

AF:

0.0766

Gnomad ASJ

AF:

0.0709

Gnomad EAS

AF:

0.0328

Gnomad SAS

AF:

0.0356

Gnomad FIN

AF:

0.123

Gnomad MID

AF:

0.0732

Gnomad NFE

AF:

0.108

Gnomad OTH

AF:

0.0901

GnomAD4 exome

AF:

0.0970

AC:

141500

AN:

1458916

Hom.:

7458

Cov.:

AF XY:

0.0953

AC XY:

69163

AN XY:

725834

show subpopulations

Gnomad4 AFR exome

AF:

0.134

Gnomad4 AMR exome

AF:

0.0521

Gnomad4 ASJ exome

AF:

0.0793

Gnomad4 EAS exome

AF:

0.0337

Gnomad4 SAS exome

AF:

0.0381

Gnomad4 FIN exome

AF:

0.122

Gnomad4 NFE exome

AF:

0.104

Gnomad4 OTH exome

AF:

0.0954

GnomAD4 genome

AF:

0.105

AC:

15922

AN:

151082

Hom.:

952

Cov.:

AF XY:

0.103

AC XY:

7649

AN XY:

73904

show subpopulations

Gnomad4 AFR

AF:

0.128

Gnomad4 AMR

AF:

0.0766

Gnomad4 ASJ

AF:

0.0709

Gnomad4 EAS

AF:

0.0328

Gnomad4 SAS

AF:

0.0355

Gnomad4 FIN

AF:

0.123

Gnomad4 NFE

AF:

0.108

Gnomad4 OTH

AF:

0.0891

Alfa

AF:

0.0462

Hom.:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 20, 2021

- -

Isolated congenital growth hormone deficiency

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Benign

0.79

Splicing

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