1-71866132-T-G

Variant names:

• chr1-71866132-T-G
• rs591540
• NM_173808.3:c.409+68947A>C

Variant summary

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

The NM_173808.3(NEGR1):​c.409+68947A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.599 in 151,706 control chromosomes in the GnomAD database, including 28,298 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 0.60 (28298 hom., cov: 32)
• Consequence: NEGR1 NM_173808.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.447
• Publications: 2 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.769 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173808.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEGR1	NM_173808.3	MANE Select	c.409+68947A>C		intron	N/A	NP_776169.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEGR1	ENST00000357731.10	TSL:1 MANE Select	c.409+68947A>C		intron	N/A	ENSP00000350364.4
	NEGR1	ENST00000306821.3	TSL:1	c.25+68947A>C		intron	N/A	ENSP00000305938.3
	NEGR1	ENST00000467479.1	TSL:5	n.406+68947A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.599 AC: 90723 AN: 151582 Hom.: 28252 Cov.: 32

Gnomad AFR AF: 0.776

Gnomad AMI AF: 0.501

Gnomad AMR AF: 0.596

Gnomad ASJ AF: 0.429

Gnomad EAS AF: 0.726

Gnomad SAS AF: 0.516

Gnomad FIN AF: 0.560

Gnomad MID AF: 0.514

Gnomad NFE AF: 0.504

Gnomad OTH AF: 0.578

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

GnomAD4 genome AF: 0.599 AC: 90840 AN: 151706 Hom.: 28298 Cov.: 32 AF XY: 0.600 AC XY: 44481 AN XY: 74140

African (AFR) AF: 0.776 AC: 32190 AN: 41460

American (AMR) AF: 0.597 AC: 9087 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.429 AC: 1481 AN: 3454

East Asian (EAS) AF: 0.726 AC: 3744 AN: 5154

South Asian (SAS) AF: 0.516 AC: 2478 AN: 4806

European-Finnish (FIN) AF: 0.560 AC: 5876 AN: 10496

Middle Eastern (MID) AF: 0.508 AC: 135 AN: 266

European-Non Finnish (NFE) AF: 0.504 AC: 34184 AN: 67840

Other (OTH) AF: 0.578 AC: 1209 AN: 2092

Alfa AF: 0.532 Hom.: 49296

Bravo AF: 0.615

Asia WGS AF: 0.640 AC: 2208 AN: 3448

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.62
DANN	Benign	0.39
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: rs591540; hg19: chr1-72331815; COSMIC: COSV60835843;