rs3785931

chr17-49500756-T-Cchr17-49500756-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002507.4(NGFR):c.67-1307T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 152,026 control chromosomes in the GnomAD database, including 12,043 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 0.37 (12043 hom., cov: 32)
• Consequence: NGFR NM_002507.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.14

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.573 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NGFR	NM_002507.4	c.67-1307T>C		intron_variant		ENST00000172229.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NGFR	ENST00000172229.8	c.67-1307T>C		intron_variant		1	NM_002507.4	P1
NGFR	ENST00000504201.1	c.-216-1307T>C		intron_variant		2
NGFR	ENST00000509200.5	c.-216-1307T>C		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.371 AC: 56313 AN: 151908 Hom.: 12026 Cov.: 32

Gnomad AFR AF: 0.579

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.414

Gnomad EAS AF: 0.447

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.377

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

GnomAD4 genome AF: 0.371 AC: 56377 AN: 152026 Hom.: 12043 Cov.: 32 AF XY: 0.371 AC XY: 27587 AN XY: 74298

Gnomad4 AFR AF: 0.579

Gnomad4 AMR AF: 0.407

Gnomad4 ASJ AF: 0.414

Gnomad4 EAS AF: 0.447

Gnomad4 SAS AF: 0.278

Gnomad4 FIN AF: 0.239

Gnomad4 NFE AF: 0.257

Gnomad4 OTH AF: 0.375

Alfa AF: 0.288 Hom.: 6025

Bravo AF: 0.393

Asia WGS AF: 0.379 AC: 1320 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	10
Dann	Benign	0.60

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: rs3785931; hg19: chr17-47578118;