17-49514328-T-C

Variant names:

• chr17-49514328-T-C
• rs741071
• NM_002507.4:c.*1319T>C

Variant summary

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

The NM_002507.4(NGFR):​c.*1319T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 154,072 control chromosomes in the GnomAD database, including 21,672 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 0.52 (21345 hom., cov: 33)
  • Exomes 𝑓: 0.57 (327 hom.)
• Consequence: NGFR NM_002507.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.834
• Publications: 16 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.665 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.*1319T>C		3_prime_UTR	Exon 6 of 6	NP_002498.1
	NGFR-AS1	NR_103773.1		n.247-3215A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NGFR	ENST00000172229.8	TSL:1 MANE Select	c.*1319T>C		3_prime_UTR	Exon 6 of 6	ENSP00000172229.3
	NGFR-AS1	ENST00000514506.1	TSL:2	n.247-3215A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.524 AC: 79602 AN: 151934 Hom.: 21334 Cov.: 33

Gnomad AFR AF: 0.418

Gnomad AMI AF: 0.528

Gnomad AMR AF: 0.499

Gnomad ASJ AF: 0.451

Gnomad EAS AF: 0.609

Gnomad SAS AF: 0.683

Gnomad FIN AF: 0.554

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.576

Gnomad OTH AF: 0.521

GnomAD4 exome AF: 0.572 AC: 1155 AN: 2020 Hom.: 327 Cov.: 0 AF XY: 0.562 AC XY: 629 AN XY: 1120

African (AFR) AF: 0.389 AC: 28 AN: 72

American (AMR) AF: 0.571 AC: 16 AN: 28

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 6 AN: 30

East Asian (EAS) AF: 0.624 AC: 131 AN: 210

South Asian (SAS) AF: 0.857 AC: 12 AN: 14

European-Finnish (FIN) AF: 0.542 AC: 129 AN: 238

Middle Eastern (MID) AF: 0.500 AC: 5 AN: 10

European-Non Finnish (NFE) AF: 0.584 AC: 765 AN: 1310

Other (OTH) AF: 0.583 AC: 63 AN: 108

GnomAD4 genome AF: 0.524 AC: 79641 AN: 152052 Hom.: 21345 Cov.: 33 AF XY: 0.526 AC XY: 39116 AN XY: 74312

African (AFR) AF: 0.418 AC: 17319 AN: 41464

American (AMR) AF: 0.499 AC: 7624 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.451 AC: 1566 AN: 3472

East Asian (EAS) AF: 0.609 AC: 3140 AN: 5160

South Asian (SAS) AF: 0.684 AC: 3306 AN: 4832

European-Finnish (FIN) AF: 0.554 AC: 5853 AN: 10560

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.576 AC: 39145 AN: 67956

Other (OTH) AF: 0.520 AC: 1100 AN: 2114

Alfa AF: 0.555 Hom.: 86371

Bravo AF: 0.511

Asia WGS AF: 0.639 AC: 2223 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.38
DANN	Benign	0.29
PhyloP100		-0.83
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: rs741071; hg19: chr17-47591690; COSMIC: COSV50804955; COSMIC: COSV50804955;