rs2665802

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

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

The NM_000515.5(GH1):​c.456+90T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 1,613,692 control chromosomes in the GnomAD database, including 125,177 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (9221 hom., cov: 32)
  • Exomes 𝑓: 0.39 (115956 hom.)
• Consequence: GH1 NM_000515.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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), Orphanet, Ambry Genetics
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 17-63917670-A-T is Benign according to our data. Variant chr17-63917670-A-T is described in ClinVar as Benign. ClinVar VariationId is 1293215.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.411 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GH1	NM_000515.5	MANE Select	c.456+90T>A		intron	N/A	NP_000506.2
	GH1	NM_022559.4		c.411+90T>A		intron	N/A	NP_072053.1	B1A4G7
	GH1	NM_022560.4		c.336+90T>A		intron	N/A	NP_072054.1	P01241-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GH1	ENST00000323322.10	TSL:1 MANE Select	c.456+90T>A		intron	N/A	ENSP00000312673.5	P01241-1
	ENSG00000285947	ENST00000647774.1		c.732+90T>A		intron	N/A	ENSP00000497443.1	A0A3B3ISS9
	GH1	ENST00000458650.6	TSL:1	c.411+90T>A		intron	N/A	ENSP00000408486.2	P01241-2

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48984 AN: 151980 Hom.: 9216 Cov.: 32

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.525

Gnomad AMR AF: 0.353

Gnomad ASJ AF: 0.440

Gnomad EAS AF: 0.410

Gnomad SAS AF: 0.267

Gnomad FIN AF: 0.409

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.415

Gnomad OTH AF: 0.355

GnomAD4 exome AF: 0.394 AC: 575572 AN: 1461594 Hom.: 115956 Cov.: 64 AF XY: 0.392 AC XY: 284997 AN XY: 727118

African (AFR) AF: 0.103 AC: 3461 AN: 33478

American (AMR) AF: 0.368 AC: 16441 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.454 AC: 11862 AN: 26134

East Asian (EAS) AF: 0.413 AC: 16403 AN: 39700

South Asian (SAS) AF: 0.281 AC: 24268 AN: 86252

European-Finnish (FIN) AF: 0.399 AC: 21294 AN: 53416

Middle Eastern (MID) AF: 0.392 AC: 2262 AN: 5764

European-Non Finnish (NFE) AF: 0.410 AC: 455974 AN: 1111742

Other (OTH) AF: 0.391 AC: 23607 AN: 60386

GnomAD4 genome AF: 0.322 AC: 49007 AN: 152098 Hom.: 9221 Cov.: 32 AF XY: 0.321 AC XY: 23881 AN XY: 74358

African (AFR) AF: 0.115 AC: 4781 AN: 41506

American (AMR) AF: 0.353 AC: 5400 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.440 AC: 1529 AN: 3472

East Asian (EAS) AF: 0.410 AC: 2122 AN: 5180

South Asian (SAS) AF: 0.269 AC: 1295 AN: 4818

European-Finnish (FIN) AF: 0.409 AC: 4321 AN: 10566

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.415 AC: 28221 AN: 67962

Other (OTH) AF: 0.358 AC: 755 AN: 2110

Alfa AF: 0.249 Hom.: 662

Bravo AF: 0.314

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.60
DANN	Benign	0.90
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

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; COSMIC: COSV60110519;