rs7523654

Positions:

• chr1-115318644-T-C

Variant summary

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

The NM_002506.3(NGF):​c.-137+19560A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 152,036 control chromosomes in the GnomAD database, including 25,917 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 0.55 (25917 hom., cov: 32)
• Consequence: NGF NM_002506.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.601

Genes affected

NGF (HGNC:7808): (nerve growth factor) This gene is a member of the NGF-beta family and encodes a secreted protein which homodimerizes and is incorporated into a larger complex. This protein has nerve growth stimulating activity and the complex is involved in the regulation of growth and the differentiation of sympathetic and certain sensory neurons. Mutations in this gene have been associated with hereditary sensory and autonomic neuropathy, type 5 (HSAN5), and dysregulation of this gene's expression is associated with allergic rhinitis. [provided by RefSeq, Jul 2008]

NGF-AS1 (HGNC:53922): (NGF antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.692 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NGF	NM_002506.3	c.-137+19560A>G		intron_variant		ENST00000369512.3	NP_002497.2
NGF-AS1	NR_157569.1	n.207+35404T>C		intron_variant, non_coding_transcript_variant
NGF	XM_006710663.4	c.-13+19560A>G		intron_variant			XP_006710726.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NGF	ENST00000369512.3	c.-137+19560A>G		intron_variant		1	NM_002506.3	ENSP00000358525	P1
NGF-AS1	ENST00000425449.1	n.207+35404T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.555 AC: 84285 AN: 151918 Hom.: 25908 Cov.: 32

Gnomad AFR AF: 0.296

Gnomad AMI AF: 0.625

Gnomad AMR AF: 0.566

Gnomad ASJ AF: 0.570

Gnomad EAS AF: 0.348

Gnomad SAS AF: 0.571

Gnomad FIN AF: 0.717

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.697

Gnomad OTH AF: 0.573

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

GnomAD4 genome AF: 0.555 AC: 84316 AN: 152036 Hom.: 25917 Cov.: 32 AF XY: 0.557 AC XY: 41380 AN XY: 74326

Gnomad4 AFR AF: 0.296

Gnomad4 AMR AF: 0.566

Gnomad4 ASJ AF: 0.570

Gnomad4 EAS AF: 0.348

Gnomad4 SAS AF: 0.572

Gnomad4 FIN AF: 0.717

Gnomad4 NFE AF: 0.697

Gnomad4 OTH AF: 0.569

Alfa AF: 0.598 Hom.: 6317

Bravo AF: 0.530

Asia WGS AF: 0.447 AC: 1561 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.5
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: rs7523654; hg19: chr1-115861265;