dbSNP rs2005172: ENSG00000285947:c.287-389T>G (chr17-63918895-A-C) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The ENST00000647774.1(ENSG00000285947):c.287-389T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.618 in 1,583,798 control chromosomes in the GnomAD database, including 307,098 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.63 ( 30870 hom., cov: 32)

Exomes 𝑓: 0.62 ( 276228 hom. )

Consequence

ENSG00000285947
ENST00000647774.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.721

Variant links:

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 links:

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=-0.94).

BP6

Variant 17-63918895-A-C is Benign according to our data. Variant chr17-63918895-A-C is described in ClinVar as [Benign]. Clinvar id is 1296532.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.7 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
GH1	NM_000515.5 link	c.-119T>G	upstream_gene_variant	ENST00000323322.10	NP_000506.2	P01241-1B1A4G6
GH1	NM_022559.4 link	c.-119T>G	upstream_gene_variant		NP_072053.1	P01241-2B1A4G7
GH1	NM_022560.4 link	c.-119T>G	upstream_gene_variant		NP_072054.1	P01241-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000285947	ENST00000647774.1 link	c.287-389T>G		intron_variant	Intron 4 of 7			ENSP00000497443.1		A0A3B3ISS9
GH1	ENST00000323322.10 link	c.-119T>G		upstream_gene_variant		1	NM_000515.5	ENSP00000312673.5		P01241-1

Frequencies

GnomAD3 genomes

AF:

0.632

AC:

95463

AN:

151146

Hom.:

30831

Cov.:

show subpopulations

Gnomad AFR

AF:

0.707

Gnomad AMI

AF:

0.770

Gnomad AMR

AF:

0.522

Gnomad ASJ

AF:

0.604

Gnomad EAS

AF:

0.443

Gnomad SAS

AF:

0.400

Gnomad FIN

AF:

0.580

Gnomad MID

AF:

0.722

Gnomad NFE

AF:

0.649

Gnomad OTH

AF:

0.626

GnomAD4 exome

AF:

0.617

AC:

883206

AN:

1432536

Hom.:

276228

AF XY:

0.612

AC XY:

435908

AN XY:

712224

show subpopulations

Gnomad4 AFR exome

AF:

0.711

Gnomad4 AMR exome

AF:

0.490

Gnomad4 ASJ exome

AF:

0.621

Gnomad4 EAS exome

AF:

0.445

Gnomad4 SAS exome

AF:

0.426

Gnomad4 FIN exome

AF:

0.581

Gnomad4 NFE exome

AF:

0.641

Gnomad4 OTH exome

AF:

0.606

GnomAD4 genome

AF:

0.632

AC:

95552

AN:

151262

Hom.:

30870

Cov.:

AF XY:

0.621

AC XY:

45917

AN XY:

73942

show subpopulations

Gnomad4 AFR

AF:

0.707

Gnomad4 AMR

AF:

0.521

Gnomad4 ASJ

AF:

0.604

Gnomad4 EAS

AF:

0.443

Gnomad4 SAS

AF:

0.400

Gnomad4 FIN

AF:

0.580

Gnomad4 NFE

AF:

0.649

Gnomad4 OTH

AF:

0.626

Alfa

AF:

0.522

Hom.:

1448

Bravo

AF:

0.631

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

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: 18160466, 12655556) -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

7.7

DANN

Benign

0.24

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