rs2072445

Positions:

• chr17-49510350-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000172229.8(NGFR):​c.569-62G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.092 in 1,593,668 control chromosomes in the GnomAD database, including 7,234 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 0.076 (558 hom., cov: 32)
  • Exomes 𝑓: 0.094 (6676 hom.)
• Consequence: NGFR ENST00000172229.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.117

Genes affected

NGFR (HGNC:7809): (nerve growth factor receptor) Nerve growth factor receptor contains an extracellular domain containing four 40-amino acid repeats with 6 cysteine residues at conserved positions followed by a serine/threonine-rich region, a single transmembrane domain, and a 155-amino acid cytoplasmic domain. The cysteine-rich region contains the nerve growth factor binding domain. [provided by RefSeq, Jul 2008]

NGFR-AS1 (HGNC:55555): (NGFR antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NGFR	NM_002507.4	c.569-62G>T		intron_variant		ENST00000172229.8	NP_002498.1
NGFR-AS1	NR_103773.1	n.377+633C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NGFR	ENST00000172229.8	c.569-62G>T		intron_variant		1	NM_002507.4	ENSP00000172229	P1
NGFR-AS1	ENST00000514506.1	n.377+633C>A		intron_variant, non_coding_transcript_variant		2
NGFR	ENST00000504201.1	c.287-62G>T		intron_variant		2		ENSP00000421731

Frequencies

GnomAD3 genomes AF: 0.0765 AC: 11633 AN: 152044 Hom.: 557 Cov.: 32

Gnomad AFR AF: 0.0290

Gnomad AMI AF: 0.0275

Gnomad AMR AF: 0.0856

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.0871

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.0720

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0951

Gnomad OTH AF: 0.0839

GnomAD4 exome AF: 0.0936 AC: 134914 AN: 1441506 Hom.: 6676 AF XY: 0.0951 AC XY: 67883 AN XY: 714170

Gnomad4 AFR exome AF: 0.0286

Gnomad4 AMR exome AF: 0.0883

Gnomad4 ASJ exome AF: 0.150

Gnomad4 EAS exome AF: 0.0889

Gnomad4 SAS exome AF: 0.136

Gnomad4 FIN exome AF: 0.0685

Gnomad4 NFE exome AF: 0.0923

Gnomad4 OTH exome AF: 0.0964

GnomAD4 genome AF: 0.0765 AC: 11636 AN: 152162 Hom.: 558 Cov.: 32 AF XY: 0.0767 AC XY: 5708 AN XY: 74398

Gnomad4 AFR AF: 0.0290

Gnomad4 AMR AF: 0.0855

Gnomad4 ASJ AF: 0.168

Gnomad4 EAS AF: 0.0873

Gnomad4 SAS AF: 0.131

Gnomad4 FIN AF: 0.0720

Gnomad4 NFE AF: 0.0951

Gnomad4 OTH AF: 0.0835

Alfa AF: 0.0899 Hom.: 202

Bravo AF: 0.0746

Asia WGS AF: 0.123 AC: 429 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.8
DANN	Benign	0.66

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

Publications

LitVar

Other links and lift over

dbSNP: rs2072445; hg19: chr17-47587712; COSMIC: COSV50801793; COSMIC: COSV50801793;