rs6171

Variant names:

• chr17-63918844-T-C
• rs6171
• ENST00000647774.1:c.287-338A>G

Your query was ambiguous. Multiple possible variants found:

• chr17-63918844-T-C
• chr17-63918844-T-G

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.287-338A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 1,610,114 control chromosomes in the GnomAD database, including 136,797 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.41 (12912 hom., cov: 32)
  • Exomes 𝑓: 0.41 (123885 hom.)
• Consequence: ENSG00000285947 ENST00000647774.1 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.35
• Publications: 14 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=-0.65).
• BP6: Variant 17-63918844-T-C is Benign according to our data. Variant chr17-63918844-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 369220.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.43 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GH1	NM_000515.5	c.-68A>G		upstream_gene_variant		ENST00000323322.10	NP_000506.2
GH1	NM_022559.4	c.-68A>G		upstream_gene_variant			NP_072053.1
GH1	NM_022560.4	c.-68A>G		upstream_gene_variant			NP_072054.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000285947	ENST00000647774.1	c.287-338A>G		intron_variant	Intron 4 of 7			ENSP00000497443.1
GH1	ENST00000323322.10	c.-68A>G		upstream_gene_variant		1	NM_000515.5	ENSP00000312673.5

Frequencies

GnomAD3 genomes AF: 0.408 AC: 61570 AN: 150844 Hom.: 12901 Cov.: 32

Gnomad AFR AF: 0.431

Gnomad AMI AF: 0.439

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.469

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.417

Gnomad NFE AF: 0.434

Gnomad OTH AF: 0.411

GnomAD4 exome AF: 0.408 AC: 595258 AN: 1459152 Hom.: 123885 Cov.: 44 AF XY: 0.405 AC XY: 294324 AN XY: 725914

African (AFR) AF: 0.429 AC: 14188 AN: 33076

American (AMR) AF: 0.270 AC: 12071 AN: 44634

Ashkenazi Jewish (ASJ) AF: 0.472 AC: 12328 AN: 26120

East Asian (EAS) AF: 0.293 AC: 11645 AN: 39684

South Asian (SAS) AF: 0.297 AC: 25608 AN: 86182

European-Finnish (FIN) AF: 0.356 AC: 18988 AN: 53398

Middle Eastern (MID) AF: 0.425 AC: 2447 AN: 5754

European-Non Finnish (NFE) AF: 0.426 AC: 473384 AN: 1110034

Other (OTH) AF: 0.408 AC: 24599 AN: 60270

GnomAD4 genome AF: 0.408 AC: 61619 AN: 150962 Hom.: 12912 Cov.: 32 AF XY: 0.399 AC XY: 29473 AN XY: 73802

African (AFR) AF: 0.431 AC: 17510 AN: 40630

American (AMR) AF: 0.327 AC: 4974 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.469 AC: 1625 AN: 3468

East Asian (EAS) AF: 0.306 AC: 1581 AN: 5172

South Asian (SAS) AF: 0.276 AC: 1319 AN: 4778

European-Finnish (FIN) AF: 0.359 AC: 3802 AN: 10578

Middle Eastern (MID) AF: 0.417 AC: 121 AN: 290

European-Non Finnish (NFE) AF: 0.434 AC: 29423 AN: 67830

Other (OTH) AF: 0.414 AC: 866 AN: 2092

Alfa AF: 0.277 Hom.: 673

Bravo AF: 0.405

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely 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: 12655556) -

Isolated congenital growth hormone deficiency Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.62
DANN	Benign	0.90
PhyloP100		-1.3
PromoterAI		-0.015	Neutral
Mutation Taster		=156/144	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs6171; hg19: chr17-61996204; COSMIC: COSV105177127;