1-71664478-C-T

Position:

• chr1-71664478-C-T

Variant summary

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

The NM_173808.3(NEGR1):​c.667+33530G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 151,924 control chromosomes in the GnomAD database, including 18,694 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 0.50 (18694 hom., cov: 32)
• Consequence: NEGR1 NM_173808.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17

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=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEGR1	NM_173808.3	c.667+33530G>A		intron_variant		ENST00000357731.10	NP_776169.2
NEGR1	XM_011541200.4	c.667+33530G>A		intron_variant			XP_011539502.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEGR1	ENST00000357731.10	c.667+33530G>A		intron_variant		1	NM_173808.3	ENSP00000350364.4
NEGR1	ENST00000306821.3	c.283+33530G>A		intron_variant		1		ENSP00000305938.3

Frequencies

GnomAD3 genomes AF: 0.496 AC: 75231 AN: 151806 Hom.: 18672 Cov.: 32

Gnomad AFR AF: 0.504

Gnomad AMI AF: 0.531

Gnomad AMR AF: 0.507

Gnomad ASJ AF: 0.485

Gnomad EAS AF: 0.348

Gnomad SAS AF: 0.527

Gnomad FIN AF: 0.464

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.501

Gnomad OTH AF: 0.501

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

GnomAD4 genome AF: 0.496 AC: 75296 AN: 151924 Hom.: 18694 Cov.: 32 AF XY: 0.494 AC XY: 36708 AN XY: 74248

Gnomad4 AFR AF: 0.504

Gnomad4 AMR AF: 0.506

Gnomad4 ASJ AF: 0.485

Gnomad4 EAS AF: 0.349

Gnomad4 SAS AF: 0.526

Gnomad4 FIN AF: 0.464

Gnomad4 NFE AF: 0.501

Gnomad4 OTH AF: 0.503

Alfa AF: 0.345 Hom.: 814

Bravo AF: 0.496

Asia WGS AF: 0.445 AC: 1548 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.16
DANN	Benign	0.27

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: rs2422021; hg19: chr1-72130161; COSMIC: COSV60835630;