17-63918895-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000647774.1(ENSG00000285947):​c.287-389T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000946 in 1,585,310 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000077 ( 0 hom. )

Consequence

ENSG00000285947
ENST00000647774.1 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.721
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GH1NM_000515.5 linkc.-119T>A upstream_gene_variant ENST00000323322.10 NP_000506.2 P01241-1B1A4G6
GH1NM_022559.4 linkc.-119T>A upstream_gene_variant NP_072053.1 P01241-2B1A4G7
GH1NM_022560.4 linkc.-119T>A upstream_gene_variant NP_072054.1 P01241-5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ENSG00000285947ENST00000647774.1 linkc.287-389T>A intron_variant Intron 4 of 7 ENSP00000497443.1 A0A3B3ISS9
GH1ENST00000323322.10 linkc.-119T>A upstream_gene_variant 1 NM_000515.5 ENSP00000312673.5 P01241-1

Frequencies

GnomAD3 genomes
AF:
0.0000265
AC:
4
AN:
151188
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000983
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000767
AC:
11
AN:
1434122
Hom.:
0
AF XY:
0.00000561
AC XY:
4
AN XY:
712992
show subpopulations
Gnomad4 AFR exome
AF:
0.0000311
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000255
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000823
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000265
AC:
4
AN:
151188
Hom.:
0
Cov.:
32
AF XY:
0.0000406
AC XY:
3
AN XY:
73838
show subpopulations
Gnomad4 AFR
AF:
0.0000983
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.91
CADD
Benign
7.6
DANN
Benign
0.16

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.

Other links and lift over

dbSNP: rs2005172; hg19: chr17-61996255; API