chr1-72256901-A-G

Variant names:

• chr1-72256901-A-G
• rs10493495
• NM_173808.3:c.176+25418T>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.176+25418T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0487 in 152,250 control chromosomes in the GnomAD database, including 304 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 0.049 (304 hom., cov: 32)
• Consequence: NEGR1 NM_173808.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.282
• 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=-0.73).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEGR1	NM_173808.3	c.176+25418T>C		intron_variant	Intron 1 of 6	ENST00000357731.10	NP_776169.2
NEGR1	XM_011541200.4	c.176+25418T>C		intron_variant	Intron 1 of 6		XP_011539502.1
NEGR1	XM_011541201.4	c.176+25418T>C		intron_variant	Intron 1 of 4		XP_011539503.1
NEGR1	XM_017000961.3	c.176+25418T>C		intron_variant	Intron 1 of 4		XP_016856450.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEGR1	ENST00000357731.10	c.176+25418T>C		intron_variant	Intron 1 of 6	1	NM_173808.3	ENSP00000350364.4

Frequencies

GnomAD3 genomes AF: 0.0488 AC: 7417 AN: 152132 Hom.: 307 Cov.: 32

Gnomad AFR AF: 0.0859

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0830

Gnomad ASJ AF: 0.0259

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.0976

Gnomad FIN AF: 0.0136

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0137

Gnomad OTH AF: 0.0463

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

GnomAD4 genome AF: 0.0487 AC: 7414 AN: 152250 Hom.: 304 Cov.: 32 AF XY: 0.0513 AC XY: 3822 AN XY: 74438

African (AFR) AF: 0.0858 AC: 3559 AN: 41504

American (AMR) AF: 0.0829 AC: 1269 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0259 AC: 90 AN: 3472

East Asian (EAS) AF: 0.165 AC: 852 AN: 5172

South Asian (SAS) AF: 0.0975 AC: 471 AN: 4830

European-Finnish (FIN) AF: 0.0136 AC: 144 AN: 10614

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0137 AC: 931 AN: 68032

Other (OTH) AF: 0.0449 AC: 95 AN: 2116

Alfa AF: 0.0299 Hom.: 401

Bravo AF: 0.0545

Asia WGS AF: 0.109 AC: 378 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	7.8
DANN	Benign	0.89
PhyloP100		0.28
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: rs10493495; hg19: chr1-72722584;