rs10789322

Positions:

• chr1-71713245-G-A
• chr1-71713245-G-T

Variant summary

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

The NM_173808.3(NEGR1):​c.536-15106C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 151,970 control chromosomes in the GnomAD database, including 8,764 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 0.31 (8764 hom., cov: 32)
• Consequence: NEGR1 NM_173808.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.271

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.555 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEGR1	NM_173808.3	c.536-15106C>T		intron_variant		ENST00000357731.10	NP_776169.2
NEGR1	XM_011541200.4	c.536-15106C>T		intron_variant			XP_011539502.1
NEGR1	XM_011541201.4	c.536-15106C>T		intron_variant			XP_011539503.1
NEGR1	XM_017000961.3	c.536-15106C>T		intron_variant			XP_016856450.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEGR1	ENST00000357731.10	c.536-15106C>T		intron_variant		1	NM_173808.3	ENSP00000350364	P1
NEGR1	ENST00000306821.3	c.152-15106C>T		intron_variant		1		ENSP00000305938
NEGR1	ENST00000467479.1	n.533-15106C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47147 AN: 151852 Hom.: 8765 Cov.: 32

Gnomad AFR AF: 0.0979

Gnomad AMI AF: 0.305

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.391

Gnomad EAS AF: 0.572

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.420

Gnomad MID AF: 0.318

Gnomad NFE AF: 0.373

Gnomad OTH AF: 0.323

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

GnomAD4 genome AF: 0.310 AC: 47157 AN: 151970 Hom.: 8764 Cov.: 32 AF XY: 0.317 AC XY: 23508 AN XY: 74254

Gnomad4 AFR AF: 0.0977

Gnomad4 AMR AF: 0.429

Gnomad4 ASJ AF: 0.391

Gnomad4 EAS AF: 0.572

Gnomad4 SAS AF: 0.303

Gnomad4 FIN AF: 0.420

Gnomad4 NFE AF: 0.373

Gnomad4 OTH AF: 0.323

Alfa AF: 0.306 Hom.: 1237

Bravo AF: 0.309

Asia WGS AF: 0.409 AC: 1418 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.5
DANN	Benign	0.78

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: rs10789322; hg19: chr1-72178928;