rs12141391

Positions:

• chr1-71808790-C-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 35 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEGR1	NM_173808.3	c.410-32493G>T		intron_variant		ENST00000357731.10
NEGR1-IT1	NR_046218.1	n.34-10520G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEGR1	ENST00000357731.10	c.410-32493G>T		intron_variant		1	NM_173808.3	P1
NEGR1	ENST00000306821.3	c.26-32493G>T		intron_variant		1
NEGR1-IT1	ENST00000453121.1	n.34-10520G>T		intron_variant, non_coding_transcript_variant		1
NEGR1	ENST00000467479.1	n.407-32493G>T		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.00533

Gnomad4 AMR AF: 0.0117

Gnomad4 ASJ AF: 0.00634

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00624

Gnomad4 FIN AF: 0.0412

Gnomad4 NFE AF: 0.0277

Gnomad4 OTH AF: 0.0157

Alfa AF: 0.0245 Hom.: 76

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

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: rs12141391; hg19: chr1-72274473;