17-49499986-A-G

Variant names:

• chr17-49499986-A-G
• rs9908234
• NM_002507.4:c.67-2077A>G

Variant summary

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

The NM_002507.4(NGFR):​c.67-2077A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 151,408 control chromosomes in the GnomAD database, including 2,859 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 0.16 (2859 hom., cov: 31)
• Consequence: NGFR NM_002507.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.924
• Publications: 17 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.315 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.67-2077A>G		intron	N/A	NP_002498.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NGFR	ENST00000172229.8	TSL:1 MANE Select	c.67-2077A>G		intron	N/A	ENSP00000172229.3
	NGFR	ENST00000504201.1	TSL:2	c.-216-2077A>G		intron	N/A	ENSP00000421731.1
	NGFR	ENST00000509200.5	TSL:4	c.-216-2077A>G		intron	N/A	ENSP00000421514.1

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23626 AN: 151292 Hom.: 2855 Cov.: 31

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.229

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.0450

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0647

Gnomad OTH AF: 0.145

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.156 AC: 23661 AN: 151408 Hom.: 2859 Cov.: 31 AF XY: 0.158 AC XY: 11665 AN XY: 74010

African (AFR) AF: 0.319 AC: 13114 AN: 41084

American (AMR) AF: 0.198 AC: 2999 AN: 15160

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 449 AN: 3462

East Asian (EAS) AF: 0.230 AC: 1185 AN: 5154

South Asian (SAS) AF: 0.142 AC: 682 AN: 4792

European-Finnish (FIN) AF: 0.0450 AC: 473 AN: 10510

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0647 AC: 4392 AN: 67930

Other (OTH) AF: 0.146 AC: 308 AN: 2110

Alfa AF: 0.108 Hom.: 2911

Bravo AF: 0.175

Asia WGS AF: 0.201 AC: 700 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	6.5
DANN	Benign	0.92
PhyloP100		-0.92
Mutation Taster		=99/1	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: rs9908234; hg19: chr17-47577348;