rs2665802

Variant names:

• chr17-63917670-A-G
• rs2665802
• NM_000515.5:c.456+90T>C

Your query was ambiguous. Multiple possible variants found:

• chr17-63917670-A-G
• chr17-63917670-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000515.5(GH1):​c.456+90T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000279 in 1,613,872 control chromosomes in the GnomAD database, including 3 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 0.000039 (1 hom., cov: 32)
  • Exomes 𝑓: 0.000027 (2 hom.)
• Consequence: GH1 NM_000515.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02
• Publications: 33 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=-0.69).
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0000394 (6/152144) while in subpopulation SAS AF = 0.00124 (6/4820). AF 95% confidence interval is 0.000542. There are 1 homozygotes in GnomAd4. There are 5 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 2 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GH1	NM_000515.5	c.456+90T>C		intron_variant	Intron 4 of 4	ENST00000323322.10	NP_000506.2
GH1	NM_022559.4	c.411+90T>C		intron_variant	Intron 4 of 4		NP_072053.1
GH1	NM_022560.4	c.336+90T>C		intron_variant	Intron 3 of 3		NP_072054.1
LOC112268204	XR_002958148.2	n.388+26A>G		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GH1	ENST00000323322.10	c.456+90T>C		intron_variant	Intron 4 of 4	1	NM_000515.5	ENSP00000312673.5
ENSG00000285947	ENST00000647774.1	c.732+90T>C		intron_variant	Intron 7 of 7			ENSP00000497443.1

Frequencies

GnomAD3 genomes AF: 0.0000395 AC: 6 AN: 152026 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000267 AC: 39 AN: 1461728 Hom.: 2 Cov.: 64 AF XY: 0.0000399 AC XY: 29 AN XY: 727160

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000452 AC: 39 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111866

Other (OTH) AF: 0.00 AC: 0 AN: 60388

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152144 Hom.: 1 Cov.: 32 AF XY: 0.0000672 AC XY: 5 AN XY: 74378

African (AFR) AF: 0.00 AC: 0 AN: 41512

American (AMR) AF: 0.00 AC: 0 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10568

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67984

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.00 Hom.: 662

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.75
DANN	Benign	0.88
PhyloP100		-1.0

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

Other links and lift over

dbSNP: rs2665802; hg19: chr17-61995030;