rs741073

Variant names:

• chr17-49514524-G-A
• rs741073
• NM_002507.4:c.*1515G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_002507.4(NGFR):​c.*1515G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 152,060 control chromosomes in the GnomAD database, including 8,655 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 0.32 (8649 hom., cov: 32)
  • Exomes 𝑓: 0.33 (6 hom.)
• Consequence: NGFR NM_002507.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.52
• 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]

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

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.452 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NGFR	NM_002507.4	MANE Select	c.*1515G>A		3_prime_UTR	Exon 6 of 6	NP_002498.1	P08138-1
	NGFR-AS1	NR_103773.1		n.247-3411C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NGFR	ENST00000172229.8	TSL:1 MANE Select	c.*1515G>A		3_prime_UTR	Exon 6 of 6	ENSP00000172229.3	P08138-1
	NGFR-AS1	ENST00000514506.1	TSL:2	n.247-3411C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.324 AC: 49236 AN: 151862 Hom.: 8635 Cov.: 32

Gnomad AFR AF: 0.457

Gnomad AMI AF: 0.398

Gnomad AMR AF: 0.304

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.237

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.285

GnomAD4 exome AF: 0.325 AC: 26 AN: 80 Hom.: 6 Cov.: 0 AF XY: 0.308 AC XY: 16 AN XY: 52

African (AFR) AF: 0.250 AC: 1 AN: 4

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.300 AC: 3 AN: 10

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.308 AC: 16 AN: 52

Other (OTH) AF: 0.600 AC: 6 AN: 10

GnomAD4 genome AF: 0.324 AC: 49299 AN: 151980 Hom.: 8649 Cov.: 32 AF XY: 0.326 AC XY: 24191 AN XY: 74270

African (AFR) AF: 0.457 AC: 18959 AN: 41474

American (AMR) AF: 0.305 AC: 4657 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 764 AN: 3468

East Asian (EAS) AF: 0.237 AC: 1213 AN: 5126

South Asian (SAS) AF: 0.379 AC: 1825 AN: 4810

European-Finnish (FIN) AF: 0.279 AC: 2953 AN: 10574

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.264 AC: 17905 AN: 67932

Other (OTH) AF: 0.285 AC: 601 AN: 2106

Alfa AF: 0.294 Hom.: 3992

Bravo AF: 0.330

Asia WGS AF: 0.334 AC: 1159 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	17
DANN	Benign	0.88
PhyloP100		1.5
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: rs741073; hg19: chr17-47591886;