rs6172

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000323322.10(GH1):​c.-38A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0237 in 1,613,064 control chromosomes in the GnomAD database, including 548 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.021 ( 42 hom., cov: 32)
Exomes 𝑓: 0.024 ( 506 hom. )

Consequence

GH1
ENST00000323322.10 5_prime_UTR

Scores

2

Clinical Significance

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

Conservation

PhyloP100: -0.334
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BP6
Variant 17-63918814-T-G is Benign according to our data. Variant chr17-63918814-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 891384.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0215 (3270/152178) while in subpopulation NFE AF= 0.0267 (1818/67988). AF 95% confidence interval is 0.0257. There are 42 homozygotes in gnomad4. There are 1541 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 42 AD,AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GH1NM_000515.5 linkuse as main transcriptc.-38A>C 5_prime_UTR_variant 1/5 ENST00000323322.10 NP_000506.2
GH1NM_022559.4 linkuse as main transcriptc.-38A>C 5_prime_UTR_variant 1/5 NP_072053.1
GH1NM_022560.4 linkuse as main transcriptc.-38A>C 5_prime_UTR_variant 1/4 NP_072054.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GH1ENST00000323322.10 linkuse as main transcriptc.-38A>C 5_prime_UTR_variant 1/51 NM_000515.5 ENSP00000312673 P1P01241-1

Frequencies

GnomAD3 genomes
AF:
0.0215
AC:
3262
AN:
152060
Hom.:
42
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0153
Gnomad AMI
AF:
0.0428
Gnomad AMR
AF:
0.0229
Gnomad ASJ
AF:
0.0450
Gnomad EAS
AF:
0.00231
Gnomad SAS
AF:
0.0157
Gnomad FIN
AF:
0.0124
Gnomad MID
AF:
0.0190
Gnomad NFE
AF:
0.0267
Gnomad OTH
AF:
0.0201
GnomAD3 exomes
AF:
0.0197
AC:
4953
AN:
250918
Hom.:
70
AF XY:
0.0199
AC XY:
2701
AN XY:
135628
show subpopulations
Gnomad AFR exome
AF:
0.0125
Gnomad AMR exome
AF:
0.0207
Gnomad ASJ exome
AF:
0.0377
Gnomad EAS exome
AF:
0.00256
Gnomad SAS exome
AF:
0.0146
Gnomad FIN exome
AF:
0.0116
Gnomad NFE exome
AF:
0.0245
Gnomad OTH exome
AF:
0.0229
GnomAD4 exome
AF:
0.0240
AC:
35033
AN:
1460886
Hom.:
506
Cov.:
35
AF XY:
0.0238
AC XY:
17274
AN XY:
726764
show subpopulations
Gnomad4 AFR exome
AF:
0.0136
Gnomad4 AMR exome
AF:
0.0208
Gnomad4 ASJ exome
AF:
0.0413
Gnomad4 EAS exome
AF:
0.00204
Gnomad4 SAS exome
AF:
0.0155
Gnomad4 FIN exome
AF:
0.0124
Gnomad4 NFE exome
AF:
0.0260
Gnomad4 OTH exome
AF:
0.0233
GnomAD4 genome
AF:
0.0215
AC:
3270
AN:
152178
Hom.:
42
Cov.:
32
AF XY:
0.0207
AC XY:
1541
AN XY:
74430
show subpopulations
Gnomad4 AFR
AF:
0.0154
Gnomad4 AMR
AF:
0.0228
Gnomad4 ASJ
AF:
0.0450
Gnomad4 EAS
AF:
0.00231
Gnomad4 SAS
AF:
0.0162
Gnomad4 FIN
AF:
0.0124
Gnomad4 NFE
AF:
0.0267
Gnomad4 OTH
AF:
0.0199
Alfa
AF:
0.0232
Hom.:
4
Bravo
AF:
0.0229

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
Likely benign, criteria provided, single submitterclinical testingGeneDxJun 19, 2021See Variant Classification Assertion Criteria. -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Decreased response to growth hormone stimulation test Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 18, 2018This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.87
CADD
Benign
2.7
DANN
Benign
0.56

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.

Other links and lift over

dbSNP: rs6172; hg19: chr17-61996174; API