1-71808790-C-A

Variant names:

• chr1-71808790-C-A
• rs12141391
• NM_173808.3:c.410-32493G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_173808.3(NEGR1):​c.410-32493G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0184 in 151,958 control chromosomes in the GnomAD database, including 35 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 0.018 (35 hom., cov: 32)
• Consequence: NEGR1 NM_173808.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.467
• Publications: 10 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]

NEGR1-IT1 (HGNC:41432): (NEGR1 intronic transcript 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0184 (2802/151958) while in subpopulation NFE AF = 0.0277 (1882/67938). AF 95% confidence interval is 0.0267. There are 35 homozygotes in GnomAd4. There are 1379 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 35 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEGR1	NM_173808.3	c.410-32493G>T		intron_variant	Intron 2 of 6	ENST00000357731.10	NP_776169.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEGR1	ENST00000357731.10	c.410-32493G>T		intron_variant	Intron 2 of 6	1	NM_173808.3	ENSP00000350364.4
NEGR1	ENST00000306821.3	c.26-32493G>T		intron_variant	Intron 2 of 6	1		ENSP00000305938.3
NEGR1-IT1	ENST00000453121.1	n.34-10520G>T		intron_variant	Intron 1 of 2	1
NEGR1	ENST00000467479.1	n.407-32493G>T		intron_variant	Intron 2 of 3	5

Frequencies

GnomAD3 genomes AF: 0.0185 AC: 2802 AN: 151840 Hom.: 35 Cov.: 32

Gnomad AFR AF: 0.00535

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0117

Gnomad ASJ AF: 0.00634

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00624

Gnomad FIN AF: 0.0412

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0277

Gnomad OTH AF: 0.0158

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

GnomAD4 genome AF: 0.0184 AC: 2802 AN: 151958 Hom.: 35 Cov.: 32 AF XY: 0.0186 AC XY: 1379 AN XY: 74244

African (AFR) AF: 0.00533 AC: 221 AN: 41464

American (AMR) AF: 0.0117 AC: 178 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.00634 AC: 22 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00624 AC: 30 AN: 4804

European-Finnish (FIN) AF: 0.0412 AC: 435 AN: 10554

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0277 AC: 1882 AN: 67938

Other (OTH) AF: 0.0157 AC: 33 AN: 2106

Alfa AF: 0.0241 Hom.: 164

Bravo AF: 0.0160

Asia WGS AF: 0.00231 AC: 8 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.1
DANN	Benign	0.31
PhyloP100		0.47
Mutation Taster		=100/0	polymorphism

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: rs12141391; hg19: chr1-72274473;