rs2005172

Variant names:

• chr17-63918895-A-C
• rs2005172
• ENST00000647774.1:c.287-389T>G

Your query was ambiguous. Multiple possible variants found:

• chr17-63918895-A-C
• chr17-63918895-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.721
• Publications: 22 publications found

Genes affected

ENSG00000285947 (HGNC:):

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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GH1	NM_000515.5	c.-119T>G		upstream_gene_variant		ENST00000323322.10	NP_000506.2
GH1	NM_022559.4	c.-119T>G		upstream_gene_variant			NP_072053.1
GH1	NM_022560.4	c.-119T>G		upstream_gene_variant			NP_072054.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.632 AC: 95463 AN: 151146 Hom.: 30831 Cov.: 32

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

African (AFR) AF: 0.711 AC: 22834 AN: 32098

American (AMR) AF: 0.490 AC: 20595 AN: 42034

Ashkenazi Jewish (ASJ) AF: 0.621 AC: 15903 AN: 25608

East Asian (EAS) AF: 0.445 AC: 17407 AN: 39126

South Asian (SAS) AF: 0.426 AC: 35782 AN: 84054

European-Finnish (FIN) AF: 0.581 AC: 30674 AN: 52794

Middle Eastern (MID) AF: 0.672 AC: 3832 AN: 5700

European-Non Finnish (NFE) AF: 0.641 AC: 700271 AN: 1091838

Other (OTH) AF: 0.606 AC: 35908 AN: 59284

GnomAD4 genome AF: 0.632 AC: 95552 AN: 151262 Hom.: 30870 Cov.: 32 AF XY: 0.621 AC XY: 45917 AN XY: 73942

African (AFR) AF: 0.707 AC: 28851 AN: 40794

American (AMR) AF: 0.521 AC: 7953 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.604 AC: 2091 AN: 3460

East Asian (EAS) AF: 0.443 AC: 2283 AN: 5158

South Asian (SAS) AF: 0.400 AC: 1918 AN: 4796

European-Finnish (FIN) AF: 0.580 AC: 6129 AN: 10570

Middle Eastern (MID) AF: 0.721 AC: 212 AN: 294

European-Non Finnish (NFE) AF: 0.649 AC: 44101 AN: 67928

Other (OTH) AF: 0.626 AC: 1313 AN: 2098

Alfa AF: 0.632 Hom.: 4690

Bravo AF: 0.631

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	7.7
DANN	Benign	0.24
PhyloP100		0.72
PromoterAI		-0.0062	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2005172; hg19: chr17-61996255; COSMIC: COSV60110547;