rs12740031

Positions:

• chr1-71756804-G-A
• chr1-71756804-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173808.3(NEGR1):​c.535+19368C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 151,212 control chromosomes in the GnomAD database, including 9,921 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 0.35 (9921 hom., cov: 30)
• Consequence: NEGR1 NM_173808.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0660

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.553 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEGR1	NM_173808.3	c.535+19368C>T		intron_variant		ENST00000357731.10	NP_776169.2
NEGR1	XM_011541200.4	c.535+19368C>T		intron_variant			XP_011539502.1
NEGR1	XM_011541201.4	c.535+19368C>T		intron_variant			XP_011539503.1
NEGR1	XM_017000961.3	c.535+19368C>T		intron_variant			XP_016856450.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEGR1	ENST00000357731.10	c.535+19368C>T		intron_variant		1	NM_173808.3	ENSP00000350364	P1
NEGR1	ENST00000306821.3	c.151+19368C>T		intron_variant		1		ENSP00000305938
NEGR1	ENST00000467479.1	n.532+19368C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.355 AC: 53598 AN: 151098 Hom.: 9911 Cov.: 30

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.304

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.571

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.355

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

GnomAD4 genome AF: 0.355 AC: 53646 AN: 151212 Hom.: 9921 Cov.: 30 AF XY: 0.359 AC XY: 26530 AN XY: 73842

Gnomad4 AFR AF: 0.247

Gnomad4 AMR AF: 0.448

Gnomad4 ASJ AF: 0.394

Gnomad4 EAS AF: 0.571

Gnomad4 SAS AF: 0.304

Gnomad4 FIN AF: 0.421

Gnomad4 NFE AF: 0.376

Gnomad4 OTH AF: 0.354

Alfa AF: 0.367 Hom.: 7412

Bravo AF: 0.359

Asia WGS AF: 0.424 AC: 1471 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.5
DANN	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs12740031; hg19: chr1-72222487;