rs2001344

Variant names:

• chr17-63918647-C-G
• rs2001344
• NM_000515.5:c.10+120G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000515.5(GH1):​c.10+120G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00886 in 1,609,934 control chromosomes in the GnomAD database, including 1,003 homozygotes. 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 0.046 (533 hom., cov: 32)
  • Exomes 𝑓: 0.0049 (470 hom.)
• Consequence: GH1 NM_000515.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.234
• Publications: 2 publications found

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]

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

ENSG00000285947 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000515.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GH1	NM_000515.5	MANE Select	c.10+120G>C		intron	N/A	NP_000506.2
	GH1	NM_022559.4		c.10+120G>C		intron	N/A	NP_072053.1
	GH1	NM_022560.4		c.10+120G>C		intron	N/A	NP_072054.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GH1	ENST00000323322.10	TSL:1 MANE Select	c.10+120G>C		intron	N/A	ENSP00000312673.5
	ENSG00000285947	ENST00000647774.1		c.287-141G>C		intron	N/A	ENSP00000497443.1
	GH1	ENST00000458650.6	TSL:1	c.10+120G>C		intron	N/A	ENSP00000408486.2

Frequencies

GnomAD3 genomes AF: 0.0464 AC: 7058 AN: 152166 Hom.: 533 Cov.: 32

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0190

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000911

Gnomad OTH AF: 0.0325

GnomAD4 exome AF: 0.00493 AC: 7186 AN: 1457650 Hom.: 470 Cov.: 34 AF XY: 0.00426 AC XY: 3091 AN XY: 725238

African (AFR) AF: 0.165 AC: 5483 AN: 33328

American (AMR) AF: 0.00887 AC: 396 AN: 44664

Ashkenazi Jewish (ASJ) AF: 0.000766 AC: 20 AN: 26104

East Asian (EAS) AF: 0.00144 AC: 57 AN: 39686

South Asian (SAS) AF: 0.000743 AC: 64 AN: 86118

European-Finnish (FIN) AF: 0.0000375 AC: 2 AN: 53388

Middle Eastern (MID) AF: 0.00702 AC: 30 AN: 4272

European-Non Finnish (NFE) AF: 0.000445 AC: 494 AN: 1109958

Other (OTH) AF: 0.0106 AC: 640 AN: 60132

GnomAD4 genome AF: 0.0465 AC: 7076 AN: 152284 Hom.: 533 Cov.: 32 AF XY: 0.0448 AC XY: 3333 AN XY: 74478

African (AFR) AF: 0.160 AC: 6636 AN: 41524

American (AMR) AF: 0.0190 AC: 291 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5194

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000911 AC: 62 AN: 68030

Other (OTH) AF: 0.0322 AC: 68 AN: 2112

Alfa AF: 0.0362 Hom.: 36

Bravo AF: 0.0537

Asia WGS AF: 0.0110 AC: 39 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.2
DANN	Benign	0.59
PhyloP100		-0.23
PromoterAI		-0.0065	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2001344; hg19: chr17-61996007;