rs12024388

Variant names:

• chr1-71787894-T-C
• rs12024388
• NM_173808.3:c.410-11597A>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.410-11597A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0808 in 152,198 control chromosomes in the GnomAD database, including 667 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 0.081 (667 hom., cov: 32)
• Consequence: NEGR1 NM_173808.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.324
• Publications: 0 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 (AFR) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEGR1	NM_173808.3	c.410-11597A>G		intron_variant	Intron 2 of 6	ENST00000357731.10	NP_776169.2
NEGR1	XM_011541200.4	c.410-11597A>G		intron_variant	Intron 2 of 6		XP_011539502.1
NEGR1	XM_011541201.4	c.410-11597A>G		intron_variant	Intron 2 of 4		XP_011539503.1
NEGR1	XM_017000961.3	c.410-11597A>G		intron_variant	Intron 2 of 4		XP_016856450.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEGR1	ENST00000357731.10	c.410-11597A>G		intron_variant	Intron 2 of 6	1	NM_173808.3	ENSP00000350364.4
NEGR1	ENST00000306821.3	c.26-11597A>G		intron_variant	Intron 2 of 6	1		ENSP00000305938.3
NEGR1	ENST00000467479.1	n.407-11597A>G		intron_variant	Intron 2 of 3	5

Frequencies

GnomAD3 genomes AF: 0.0809 AC: 12297 AN: 152076 Hom.: 669 Cov.: 32

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.0650

Gnomad ASJ AF: 0.0430

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.0662

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0471

Gnomad OTH AF: 0.0624

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

GnomAD4 genome AF: 0.0808 AC: 12304 AN: 152198 Hom.: 667 Cov.: 32 AF XY: 0.0818 AC XY: 6086 AN XY: 74444

African (AFR) AF: 0.141 AC: 5853 AN: 41522

American (AMR) AF: 0.0655 AC: 1001 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0430 AC: 149 AN: 3466

East Asian (EAS) AF: 0.137 AC: 708 AN: 5176

South Asian (SAS) AF: 0.102 AC: 494 AN: 4828

European-Finnish (FIN) AF: 0.0662 AC: 702 AN: 10606

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0471 AC: 3204 AN: 67996

Other (OTH) AF: 0.0613 AC: 129 AN: 2106

Alfa AF: 0.0593 Hom.: 1164

Bravo AF: 0.0845

Asia WGS AF: 0.0870 AC: 303 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.0
DANN	Benign	0.52
PhyloP100		0.32
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: rs12024388; hg19: chr1-72253577;