1-72259661-T-C

Variant names:

• chr1-72259661-T-C
• rs9424977
• NM_173808.3:c.176+22658A>G

Variant summary

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

The NM_173808.3(NEGR1):​c.176+22658A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 151,784 control chromosomes in the GnomAD database, including 17,754 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 0.47 (17754 hom., cov: 31)
• Consequence: NEGR1 NM_173808.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.17
• Publications: 8 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173808.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEGR1	NM_173808.3	MANE Select	c.176+22658A>G		intron	N/A	NP_776169.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEGR1	ENST00000357731.10	TSL:1 MANE Select	c.176+22658A>G		intron	N/A	ENSP00000350364.4

Frequencies

GnomAD3 genomes AF: 0.475 AC: 71968 AN: 151666 Hom.: 17718 Cov.: 31

Gnomad AFR AF: 0.542

Gnomad AMI AF: 0.557

Gnomad AMR AF: 0.384

Gnomad ASJ AF: 0.376

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.368

Gnomad FIN AF: 0.444

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.496

Gnomad OTH AF: 0.449

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

GnomAD4 genome AF: 0.475 AC: 72047 AN: 151784 Hom.: 17754 Cov.: 31 AF XY: 0.466 AC XY: 34549 AN XY: 74156

African (AFR) AF: 0.543 AC: 22493 AN: 41418

American (AMR) AF: 0.383 AC: 5835 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.376 AC: 1303 AN: 3464

East Asian (EAS) AF: 0.151 AC: 776 AN: 5150

South Asian (SAS) AF: 0.367 AC: 1766 AN: 4816

European-Finnish (FIN) AF: 0.444 AC: 4688 AN: 10552

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.496 AC: 33632 AN: 67834

Other (OTH) AF: 0.444 AC: 935 AN: 2106

Alfa AF: 0.477 Hom.: 9130

Bravo AF: 0.470

Asia WGS AF: 0.292 AC: 1019 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.0040
DANN	Benign	0.47
PhyloP100		-2.2
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: rs9424977; hg19: chr1-72725344; COSMIC: COSV63240119;