rs2821238

Positions:

• chr1-72125420-C-A

Variant summary

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

The NM_173808.3(NEGR1):​c.176+156899G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.942 in 152,066 control chromosomes in the GnomAD database, including 67,695 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 0.94 (67695 hom., cov: 32)
• Consequence: NEGR1 NM_173808.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0670

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEGR1	NM_173808.3	c.176+156899G>T		intron_variant		ENST00000357731.10
NEGR1	XM_011541200.4	c.176+156899G>T		intron_variant
NEGR1	XM_011541201.4	c.176+156899G>T		intron_variant
NEGR1	XM_017000961.3	c.176+156899G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEGR1	ENST00000357731.10	c.176+156899G>T		intron_variant		1	NM_173808.3	P1

Frequencies

GnomAD3 genomes AF: 0.942 AC: 143084 AN: 151948 Hom.: 67652 Cov.: 32

Gnomad AFR AF: 0.841

Gnomad AMI AF: 0.950

Gnomad AMR AF: 0.974

Gnomad ASJ AF: 0.984

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.998

Gnomad FIN AF: 0.983

Gnomad MID AF: 0.991

Gnomad NFE AF: 0.978

Gnomad OTH AF: 0.956

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

GnomAD4 genome AF: 0.942 AC: 143184 AN: 152066 Hom.: 67695 Cov.: 32 AF XY: 0.944 AC XY: 70210 AN XY: 74344

Gnomad4 AFR AF: 0.841

Gnomad4 AMR AF: 0.974

Gnomad4 ASJ AF: 0.984

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.998

Gnomad4 FIN AF: 0.983

Gnomad4 NFE AF: 0.978

Gnomad4 OTH AF: 0.956

Alfa AF: 0.953 Hom.: 8590

Bravo AF: 0.937

Asia WGS AF: 0.990 AC: 3408 AN: 3442

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.1
DANN	Benign	0.54

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: rs2821238; hg19: chr1-72591103;