rs741073

Positions:

• chr17-49514524-G-A

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NGFR	NM_002507.4	c.*1515G>A		3_prime_UTR_variant	6/6	ENST00000172229.8
NGFR-AS1	NR_103773.1	n.247-3411C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NGFR	ENST00000172229.8	c.*1515G>A		3_prime_UTR_variant	6/6	1	NM_002507.4	P1
NGFR-AS1	ENST00000514506.1	n.247-3411C>T		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR exome AF: 0.250

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.300

Gnomad4 NFE exome AF: 0.308

Gnomad4 OTH exome AF: 0.600

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

Gnomad4 AFR AF: 0.457

Gnomad4 AMR AF: 0.305

Gnomad4 ASJ AF: 0.220

Gnomad4 EAS AF: 0.237

Gnomad4 SAS AF: 0.379

Gnomad4 FIN AF: 0.279

Gnomad4 NFE AF: 0.264

Gnomad4 OTH AF: 0.285

Alfa AF: 0.299 Hom.: 2111

Bravo AF: 0.330

Asia WGS AF: 0.334 AC: 1159 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	17
DANN	Benign	0.88

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: rs741073; hg19: chr17-47591886;