rs6659202

Positions:

• chr1-71841737-T-A

Variant summary

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

The NM_173808.3(NEGR1):​c.410-65440A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 152,122 control chromosomes in the GnomAD database, including 5,349 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 0.24 (5349 hom., cov: 32)
• Consequence: NEGR1 NM_173808.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.870

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.534 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEGR1	NM_173808.3	c.410-65440A>T		intron_variant		ENST00000357731.10	NP_776169.2
NEGR1	XM_011541200.4	c.410-65440A>T		intron_variant			XP_011539502.1
NEGR1	XM_011541201.4	c.410-65440A>T		intron_variant			XP_011539503.1
NEGR1	XM_017000961.3	c.410-65440A>T		intron_variant			XP_016856450.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEGR1	ENST00000357731.10	c.410-65440A>T		intron_variant		1	NM_173808.3	ENSP00000350364	P1
NEGR1	ENST00000306821.3	c.26-65440A>T		intron_variant		1		ENSP00000305938
NEGR1	ENST00000467479.1	n.407-65440A>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36283 AN: 152004 Hom.: 5345 Cov.: 32

Gnomad AFR AF: 0.0828

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.270

Gnomad EAS AF: 0.550

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.262

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

GnomAD4 genome AF: 0.239 AC: 36299 AN: 152122 Hom.: 5349 Cov.: 32 AF XY: 0.243 AC XY: 18080 AN XY: 74348

Gnomad4 AFR AF: 0.0828

Gnomad4 AMR AF: 0.217

Gnomad4 ASJ AF: 0.270

Gnomad4 EAS AF: 0.551

Gnomad4 SAS AF: 0.321

Gnomad4 FIN AF: 0.370

Gnomad4 NFE AF: 0.285

Gnomad4 OTH AF: 0.266

Alfa AF: 0.255 Hom.: 693

Bravo AF: 0.224

Asia WGS AF: 0.435 AC: 1511 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.11
DANN	Benign	0.32

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: rs6659202; hg19: chr1-72307420;