chr1-115338434-G-A

Variant names:

• chr1-115338434-G-A
• rs11102930
• ENST00000680752.1:c.-206C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000680752.1(NGF):​c.-206C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.545 in 151,962 control chromosomes in the GnomAD database, including 23,903 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.54 (23903 hom., cov: 32)
• Consequence: NGF ENST00000680752.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.277
• Publications: 13 publications found

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

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 1-115338434-G-A is Benign according to our data. Variant chr1-115338434-G-A is described in ClinVar as Benign. ClinVar VariationId is 667672.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.644 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000680752.1. 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
	NGF-AS1	NR_157569.1		n.208-27236G>A		intron	N/A
	NGF	NM_002506.3	MANE Select	c.-367C>T		upstream_gene	N/A	NP_002497.2
	NGF	NM_001437545.1		c.-243C>T		upstream_gene	N/A	NP_001424474.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NGF	ENST00000680752.1		c.-206C>T		5_prime_UTR	Exon 1 of 3	ENSP00000505558.1
	NGF	ENST00000679806.1		c.-137+174C>T		intron	N/A	ENSP00000506492.1
	NGF-AS1	ENST00000425449.1	TSL:2	n.208-27236G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.545 AC: 82755 AN: 151842 Hom.: 23887 Cov.: 32

Gnomad AFR AF: 0.355

Gnomad AMI AF: 0.704

Gnomad AMR AF: 0.521

Gnomad ASJ AF: 0.561

Gnomad EAS AF: 0.427

Gnomad SAS AF: 0.513

Gnomad FIN AF: 0.709

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.649

Gnomad OTH AF: 0.547

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

GnomAD4 genome AF: 0.545 AC: 82801 AN: 151962 Hom.: 23903 Cov.: 32 AF XY: 0.546 AC XY: 40532 AN XY: 74274

African (AFR) AF: 0.355 AC: 14729 AN: 41458

American (AMR) AF: 0.521 AC: 7965 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.561 AC: 1945 AN: 3466

East Asian (EAS) AF: 0.427 AC: 2189 AN: 5122

South Asian (SAS) AF: 0.513 AC: 2465 AN: 4808

European-Finnish (FIN) AF: 0.709 AC: 7504 AN: 10588

Middle Eastern (MID) AF: 0.510 AC: 149 AN: 292

European-Non Finnish (NFE) AF: 0.649 AC: 44062 AN: 67922

Other (OTH) AF: 0.544 AC: 1151 AN: 2114

Alfa AF: 0.613 Hom.: 46105

Bravo AF: 0.522

Asia WGS AF: 0.469 AC: 1633 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 20, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.5
DANN	Benign	0.49
PhyloP100		0.28
PromoterAI		-0.023	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11102930; hg19: chr1-115881055;