1-71605446-A-T

Variant names:

• chr1-71605446-A-T
• rs10493485
• NM_173808.3:c.788+5580T>A

Variant summary

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

The NM_173808.3(NEGR1):​c.788+5580T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 152,066 control chromosomes in the GnomAD database, including 6,001 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 0.25 (6001 hom., cov: 32)
• Consequence: NEGR1 NM_173808.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.847
• Publications: 14 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEGR1	NM_173808.3	c.788+5580T>A		intron_variant	Intron 5 of 6	ENST00000357731.10	NP_776169.2
NEGR1	XM_011541200.4	c.788+5580T>A		intron_variant	Intron 5 of 6		XP_011539502.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEGR1	ENST00000357731.10	c.788+5580T>A		intron_variant	Intron 5 of 6	1	NM_173808.3	ENSP00000350364.4
NEGR1	ENST00000306821.3	c.404+5580T>A		intron_variant	Intron 5 of 6	1		ENSP00000305938.3

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38194 AN: 151946 Hom.: 5995 Cov.: 32

Gnomad AFR AF: 0.0588

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.334

Gnomad EAS AF: 0.556

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.364

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.261

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

GnomAD4 genome AF: 0.251 AC: 38212 AN: 152066 Hom.: 6001 Cov.: 32 AF XY: 0.256 AC XY: 19018 AN XY: 74296

African (AFR) AF: 0.0586 AC: 2435 AN: 41534

American (AMR) AF: 0.282 AC: 4304 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.334 AC: 1158 AN: 3468

East Asian (EAS) AF: 0.555 AC: 2855 AN: 5144

South Asian (SAS) AF: 0.265 AC: 1274 AN: 4810

European-Finnish (FIN) AF: 0.364 AC: 3836 AN: 10540

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.315 AC: 21433 AN: 67976

Other (OTH) AF: 0.263 AC: 555 AN: 2114

Alfa AF: 0.320 Hom.: 4657

Bravo AF: 0.244

Asia WGS AF: 0.381 AC: 1325 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.1
DANN	Benign	0.41
PhyloP100		0.85
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: rs10493485; hg19: chr1-72071129;