chr17-49510350-G-T

Variant names:

• chr17-49510350-G-T
• rs2072445
• NM_002507.4:c.569-62G>T

Variant summary

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

The NM_002507.4(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 NM_002507.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.117
• Publications: 13 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002507.4. 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
	NGFR	NM_002507.4	MANE Select	c.569-62G>T		intron	N/A	NP_002498.1
	NGFR-AS1	NR_103773.1		n.377+633C>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NGFR	ENST00000172229.8	TSL:1 MANE Select	c.569-62G>T		intron	N/A	ENSP00000172229.3
	NGFR	ENST00000504201.1	TSL:2	c.287-62G>T		intron	N/A	ENSP00000421731.1
	NGFR-AS1	ENST00000514506.1	TSL:2	n.377+633C>A		intron	N/A

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

African (AFR) AF: 0.0286 AC: 948 AN: 33128

American (AMR) AF: 0.0883 AC: 3892 AN: 44078

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 3797 AN: 25234

East Asian (EAS) AF: 0.0889 AC: 3501 AN: 39366

South Asian (SAS) AF: 0.136 AC: 11555 AN: 84808

European-Finnish (FIN) AF: 0.0685 AC: 3414 AN: 49852

Middle Eastern (MID) AF: 0.105 AC: 595 AN: 5682

European-Non Finnish (NFE) AF: 0.0923 AC: 101476 AN: 1099834

Other (OTH) AF: 0.0964 AC: 5736 AN: 59524

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

African (AFR) AF: 0.0290 AC: 1205 AN: 41508

American (AMR) AF: 0.0855 AC: 1308 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 583 AN: 3468

East Asian (EAS) AF: 0.0873 AC: 451 AN: 5168

South Asian (SAS) AF: 0.131 AC: 631 AN: 4826

European-Finnish (FIN) AF: 0.0720 AC: 764 AN: 10606

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0951 AC: 6466 AN: 67978

Other (OTH) AF: 0.0835 AC: 176 AN: 2108

Alfa AF: 0.0908 Hom.: 520

Bravo AF: 0.0746

Asia WGS AF: 0.123 AC: 429 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.8
DANN	Benign	0.66
PhyloP100		0.12
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: rs2072445; hg19: chr17-47587712; COSMIC: COSV50801793; COSMIC: COSV50801793;