1-72279313-T-C

Position:

• chr1-72279313-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_173808.3(NEGR1):​c.176+3006A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 151,922 control chromosomes in the GnomAD database, including 19,307 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 0.49 (19307 hom., cov: 32)
• Consequence: NEGR1 NM_173808.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.180

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.828 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEGR1	NM_173808.3	c.176+3006A>G		intron_variant		ENST00000357731.10
NEGR1	XM_011541200.4	c.176+3006A>G		intron_variant
NEGR1	XM_011541201.4	c.176+3006A>G		intron_variant
NEGR1	XM_017000961.3	c.176+3006A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEGR1	ENST00000357731.10	c.176+3006A>G		intron_variant		1	NM_173808.3	P1

Frequencies

GnomAD3 genomes AF: 0.487 AC: 73918 AN: 151806 Hom.: 19288 Cov.: 32

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.444

Gnomad AMR AF: 0.604

Gnomad ASJ AF: 0.623

Gnomad EAS AF: 0.850

Gnomad SAS AF: 0.630

Gnomad FIN AF: 0.555

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.504

Gnomad OTH AF: 0.528

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

GnomAD4 genome AF: 0.487 AC: 73951 AN: 151922 Hom.: 19307 Cov.: 32 AF XY: 0.497 AC XY: 36906 AN XY: 74232

Gnomad4 AFR AF: 0.322

Gnomad4 AMR AF: 0.605

Gnomad4 ASJ AF: 0.623

Gnomad4 EAS AF: 0.849

Gnomad4 SAS AF: 0.632

Gnomad4 FIN AF: 0.555

Gnomad4 NFE AF: 0.504

Gnomad4 OTH AF: 0.533

Alfa AF: 0.505 Hom.: 25597

Bravo AF: 0.487

Asia WGS AF: 0.702 AC: 2431 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	16
DANN	Benign	0.81

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: rs1870676; hg19: chr1-72744996;