rs12024388

chr1-71787894-T-C

Variant summary

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

The NM_173808.3(NEGR1):c.410-11597A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0808 in 152,198 control chromosomes in the GnomAD database, including 667 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 0.081 (667 hom., cov: 32)
• Consequence: NEGR1 NM_173808.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.324

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEGR1	NM_173808.3	c.410-11597A>G		intron_variant		ENST00000357731.10
NEGR1	XM_011541200.4	c.410-11597A>G		intron_variant
NEGR1	XM_011541201.4	c.410-11597A>G		intron_variant
NEGR1	XM_017000961.3	c.410-11597A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEGR1	ENST00000357731.10	c.410-11597A>G		intron_variant		1	NM_173808.3	P1
NEGR1	ENST00000306821.3	c.26-11597A>G		intron_variant		1
NEGR1	ENST00000467479.1	n.407-11597A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0809 AC: 12297 AN: 152076 Hom.: 669 Cov.: 32

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.0650

Gnomad ASJ AF: 0.0430

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.0662

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0471

Gnomad OTH AF: 0.0624

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

GnomAD4 genome AF: 0.0808 AC: 12304 AN: 152198 Hom.: 667 Cov.: 32 AF XY: 0.0818 AC XY: 6086 AN XY: 74444

Gnomad4 AFR AF: 0.141

Gnomad4 AMR AF: 0.0655

Gnomad4 ASJ AF: 0.0430

Gnomad4 EAS AF: 0.137

Gnomad4 SAS AF: 0.102

Gnomad4 FIN AF: 0.0662

Gnomad4 NFE AF: 0.0471

Gnomad4 OTH AF: 0.0613

Alfa AF: 0.0525 Hom.: 405

Bravo AF: 0.0845

Asia WGS AF: 0.0870 AC: 303 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	2.0
Dann	Benign	0.52

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: rs12024388; hg19: chr1-72253577;