17-49506412-C-T

Variant names:

• chr17-49506412-C-T
• rs746284856
• NM_002507.4:c.322C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 1P and 4B. PP3 BS2

The NM_002507.4(NGFR):​c.322C>T​(p.Arg108Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000179 in 1,452,834 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: NGFR NM_002507.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.666
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.802
• BS2: High AC in GnomAdExome4 at 26 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NGFR	NM_002507.4	MANE Select	c.322C>T	p.Arg108Cys	missense	Exon 3 of 6	NP_002498.1	P08138-1
	NGFR-AS1	NR_103773.1		n.466G>A		non_coding_transcript_exon	Exon 3 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NGFR	ENST00000172229.8	TSL:1 MANE Select	c.322C>T	p.Arg108Cys	missense	Exon 3 of 6	ENSP00000172229.3	P08138-1
	NGFR	ENST00000504201.1	TSL:2	c.40C>T	p.Arg14Cys	missense	Exon 3 of 6	ENSP00000421731.1	P08138-2
	NGFR-AS1	ENST00000514506.1	TSL:2	n.466G>A		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.0000179 AC: 26 AN: 1452834 Hom.: 0 Cov.: 32 AF XY: 0.0000166 AC XY: 12 AN XY: 722840

African (AFR) AF: 0.00 AC: 0 AN: 33404

American (AMR) AF: 0.00 AC: 0 AN: 44542

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26032

East Asian (EAS) AF: 0.00 AC: 0 AN: 39594

South Asian (SAS) AF: 0.00 AC: 0 AN: 86126

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46952

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.0000234 AC: 26 AN: 1110258

Other (OTH) AF: 0.00 AC: 0 AN: 60164

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.77	D
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.95	D
M_CAP	Uncertain	0.25	D
MetaRNN	Pathogenic	0.80	D
MetaSVM	Uncertain	0.78	D
MutationAssessor	Uncertain	2.3	M
PhyloP100		0.67
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-2.3	N
REVEL	Pathogenic	0.69
Sift	Benign	0.039	D
Sift4G	Benign	0.074	T
Polyphen		1.0	D
Vest4		0.67
MutPred		0.55		Loss of sheet (P = 0.0228)
MVP		0.85
MPC		1.4
ClinPred		0.96	D
GERP RS		4.6
Varity_R		0.13
gMVP		0.91
Mutation Taster		=77/23	polymorphism

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: rs746284856; hg19: chr17-47583774;