rs988421

chr1-72084153-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.91).
• 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/exons	MANE	UniProt
NEGR1	NM_173808.3	c.177-148842G>A		intron_variant		ENST00000357731.10
NEGR1	XM_011541200.4	c.177-148842G>A		intron_variant
NEGR1	XM_011541201.4	c.177-148842G>A		intron_variant
NEGR1	XM_017000961.3	c.177-148842G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEGR1	ENST00000357731.10	c.177-148842G>A		intron_variant		1	NM_173808.3	P1
NEGR1	ENST00000306821.3	c.-209+16592G>A		intron_variant		1
NEGR1	ENST00000467479.1	n.173+16592G>A		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.386

Gnomad4 AMR AF: 0.496

Gnomad4 ASJ AF: 0.474

Gnomad4 EAS AF: 0.121

Gnomad4 SAS AF: 0.321

Gnomad4 FIN AF: 0.399

Gnomad4 NFE AF: 0.486

Gnomad4 OTH AF: 0.441

Alfa AF: 0.474 Hom.: 36258

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

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: rs988421; hg19: chr1-72549836; COSMIC: COSV60837082;