rs954299

Variant names:

• chr1-71655902-C-A
• rs954299
• NM_173808.3:c.667+42106G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-71655902-C-A
• chr1-71655902-C-G

Variant summary

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

The NM_173808.3(NEGR1):​c.667+42106G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.478 in 151,976 control chromosomes in the GnomAD database, including 17,446 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 0.48 (17446 hom., cov: 32)
• Consequence: NEGR1 NM_173808.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.57
• Publications: 4 publications found

Genes affected

NEGR1 (HGNC:17302): (neuronal growth regulator 1) Predicted to act upstream of or within several processes, including feeding behavior; locomotory behavior; and positive regulation of neuron projection development. Predicted to be located in extracellular region and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.498 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEGR1	NM_173808.3	c.667+42106G>T		intron_variant	Intron 4 of 6	ENST00000357731.10	NP_776169.2
NEGR1	XM_011541200.4	c.667+42106G>T		intron_variant	Intron 4 of 6		XP_011539502.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEGR1	ENST00000357731.10	c.667+42106G>T		intron_variant	Intron 4 of 6	1	NM_173808.3	ENSP00000350364.4
NEGR1	ENST00000306821.3	c.283+42106G>T		intron_variant	Intron 4 of 6	1		ENSP00000305938.3

Frequencies

GnomAD3 genomes AF: 0.478 AC: 72600 AN: 151858 Hom.: 17435 Cov.: 32

Gnomad AFR AF: 0.504

Gnomad AMI AF: 0.530

Gnomad AMR AF: 0.442

Gnomad ASJ AF: 0.474

Gnomad EAS AF: 0.348

Gnomad SAS AF: 0.481

Gnomad FIN AF: 0.449

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.484

Gnomad OTH AF: 0.480

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

GnomAD4 genome AF: 0.478 AC: 72648 AN: 151976 Hom.: 17446 Cov.: 32 AF XY: 0.477 AC XY: 35414 AN XY: 74286

African (AFR) AF: 0.504 AC: 20893 AN: 41450

American (AMR) AF: 0.441 AC: 6724 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.474 AC: 1643 AN: 3468

East Asian (EAS) AF: 0.349 AC: 1803 AN: 5166

South Asian (SAS) AF: 0.481 AC: 2322 AN: 4830

European-Finnish (FIN) AF: 0.449 AC: 4737 AN: 10550

Middle Eastern (MID) AF: 0.541 AC: 158 AN: 292

European-Non Finnish (NFE) AF: 0.484 AC: 32878 AN: 67944

Other (OTH) AF: 0.479 AC: 1009 AN: 2108

Alfa AF: 0.479 Hom.: 48940

Bravo AF: 0.473

Asia WGS AF: 0.421 AC: 1464 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	0.054
DANN	Benign	0.50
PhyloP100		-2.6
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: rs954299; hg19: chr1-72121585; COSMIC: COSV60835528;