rs954299

chr1-71655902-C-Achr1-71655902-C-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
NEGR1	NM_173808.3	c.667+42106G>T		intron_variant		ENST00000357731.10
NEGR1	XM_011541200.4	c.667+42106G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEGR1	ENST00000357731.10	c.667+42106G>T		intron_variant		1	NM_173808.3	P1
NEGR1	ENST00000306821.3	c.283+42106G>T		intron_variant		1

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

Gnomad4 AFR AF: 0.504

Gnomad4 AMR AF: 0.441

Gnomad4 ASJ AF: 0.474

Gnomad4 EAS AF: 0.349

Gnomad4 SAS AF: 0.481

Gnomad4 FIN AF: 0.449

Gnomad4 NFE AF: 0.484

Gnomad4 OTH AF: 0.479

Alfa AF: 0.480 Hom.: 29436

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

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: rs954299; hg19: chr1-72121585; COSMIC: COSV60835528;