rs988421

Variant names:

• chr1-72084153-C-T
• rs988421
• NM_173808.3:c.177-148842G>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.177-148842G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.436 in 151,782 control chromosomes in the GnomAD database, including 14,891 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 0.44 (14891 hom., cov: 31)
• Consequence: NEGR1 NM_173808.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.217
• Publications: 5 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.486 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEGR1	NM_173808.3	c.177-148842G>A		intron_variant	Intron 1 of 6	ENST00000357731.10	NP_776169.2
NEGR1	XM_011541200.4	c.177-148842G>A		intron_variant	Intron 1 of 6		XP_011539502.1
NEGR1	XM_011541201.4	c.177-148842G>A		intron_variant	Intron 1 of 4		XP_011539503.1
NEGR1	XM_017000961.3	c.177-148842G>A		intron_variant	Intron 1 of 4		XP_016856450.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEGR1	ENST00000357731.10	c.177-148842G>A		intron_variant	Intron 1 of 6	1	NM_173808.3	ENSP00000350364.4
NEGR1	ENST00000306821.3	c.-209+16592G>A		intron_variant	Intron 1 of 6	1		ENSP00000305938.3
NEGR1	ENST00000467479.1	n.173+16592G>A		intron_variant	Intron 1 of 3	5

Frequencies

GnomAD3 genomes AF: 0.436 AC: 66085 AN: 151664 Hom.: 14889 Cov.: 31

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.568

Gnomad AMR AF: 0.496

Gnomad ASJ AF: 0.474

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.399

Gnomad MID AF: 0.474

Gnomad NFE AF: 0.486

Gnomad OTH AF: 0.443

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

GnomAD4 genome AF: 0.436 AC: 66119 AN: 151782 Hom.: 14891 Cov.: 31 AF XY: 0.426 AC XY: 31585 AN XY: 74174

African (AFR) AF: 0.386 AC: 15949 AN: 41360

American (AMR) AF: 0.496 AC: 7558 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.474 AC: 1644 AN: 3466

East Asian (EAS) AF: 0.121 AC: 625 AN: 5154

South Asian (SAS) AF: 0.321 AC: 1544 AN: 4804

European-Finnish (FIN) AF: 0.399 AC: 4195 AN: 10524

Middle Eastern (MID) AF: 0.466 AC: 135 AN: 290

European-Non Finnish (NFE) AF: 0.486 AC: 33025 AN: 67922

Other (OTH) AF: 0.441 AC: 926 AN: 2102

Alfa AF: 0.470 Hom.: 54575

Bravo AF: 0.443

Asia WGS AF: 0.260 AC: 904 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.63
PhyloP100		-0.22
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: rs988421; hg19: chr1-72549836; COSMIC: COSV60837082;