1-71605446-A-T

Position:

• chr1-71605446-A-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.85).
• 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/exons	MANE	UniProt
NEGR1	NM_173808.3	c.788+5580T>A		intron_variant		ENST00000357731.10
NEGR1	XM_011541200.4	c.788+5580T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEGR1	ENST00000357731.10	c.788+5580T>A		intron_variant		1	NM_173808.3	P1
NEGR1	ENST00000306821.3	c.404+5580T>A		intron_variant		1

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

Gnomad4 AFR AF: 0.0586

Gnomad4 AMR AF: 0.282

Gnomad4 ASJ AF: 0.334

Gnomad4 EAS AF: 0.555

Gnomad4 SAS AF: 0.265

Gnomad4 FIN AF: 0.364

Gnomad4 NFE AF: 0.315

Gnomad4 OTH AF: 0.263

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

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: rs10493485; hg19: chr1-72071129;