chr1-71638764-C-T

Variant names:

• chr1-71638764-C-T
• rs1041676
• NM_173808.3:c.668-27618G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173808.3(NEGR1):​c.668-27618G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 151,696 control chromosomes in the GnomAD database, including 5,881 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 0.25 (5881 hom., cov: 31)
• Consequence: NEGR1 NM_173808.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.446
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.464 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEGR1	NM_173808.3	c.668-27618G>A		intron_variant	Intron 4 of 6	ENST00000357731.10	NP_776169.2
NEGR1	XM_011541200.4	c.668-27618G>A		intron_variant	Intron 4 of 6		XP_011539502.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEGR1	ENST00000357731.10	c.668-27618G>A		intron_variant	Intron 4 of 6	1	NM_173808.3	ENSP00000350364.4
NEGR1	ENST00000306821.3	c.284-27618G>A		intron_variant	Intron 4 of 6	1		ENSP00000305938.3

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38124 AN: 151576 Hom.: 5882 Cov.: 31

Gnomad AFR AF: 0.0594

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.370

Gnomad EAS AF: 0.481

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.353

Gnomad MID AF: 0.264

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.279

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

GnomAD4 genome AF: 0.251 AC: 38126 AN: 151696 Hom.: 5881 Cov.: 31 AF XY: 0.254 AC XY: 18835 AN XY: 74086

African (AFR) AF: 0.0592 AC: 2454 AN: 41430

American (AMR) AF: 0.300 AC: 4564 AN: 15190

Ashkenazi Jewish (ASJ) AF: 0.370 AC: 1284 AN: 3472

East Asian (EAS) AF: 0.480 AC: 2448 AN: 5102

South Asian (SAS) AF: 0.243 AC: 1171 AN: 4810

European-Finnish (FIN) AF: 0.353 AC: 3710 AN: 10502

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.318 AC: 21597 AN: 67884

Other (OTH) AF: 0.279 AC: 586 AN: 2104

Alfa AF: 0.295 Hom.: 24027

Bravo AF: 0.244

Asia WGS AF: 0.355 AC: 1232 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.0
DANN	Benign	0.71
PhyloP100		-0.45
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1041676; hg19: chr1-72104447;