1-71698078-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_Moderate BP6_Moderate BP7

The NM_173808.3(NEGR1):c.597G>A(p.Gly199=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000422 in 1,611,158 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00027 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00044 (2 hom.)
• Consequence: NEGR1 NM_173808.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.177

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 Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BP6: Variant 1-71698078-C-T is Benign according to our data. Variant chr1-71698078-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2638876.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.177 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEGR1	NM_173808.3	c.597G>A	p.Gly199=	synonymous_variant	4/7	ENST00000357731.10
NEGR1	XM_011541200.4	c.597G>A	p.Gly199=	synonymous_variant	4/7
NEGR1	XM_011541201.4	c.597G>A	p.Gly199=	synonymous_variant	4/5
NEGR1	XM_017000961.3	c.597G>A	p.Gly199=	synonymous_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEGR1	ENST00000357731.10	c.597G>A	p.Gly199=	synonymous_variant	4/7	1	NM_173808.3	P1
NEGR1	ENST00000306821.3	c.213G>A	p.Gly71=	synonymous_variant	4/7	1
NEGR1	ENST00000467479.1	n.594G>A		non_coding_transcript_exon_variant	4/4	5
NEGR1	ENST00000478526.1	n.286G>A		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes AF: 0.000270 AC: 41 AN: 151740 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000330

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000413

Gnomad OTH AF: 0.000960

GnomAD3 exomes AF: 0.000319 AC: 80 AN: 250466 Hom.: 0 AF XY: 0.000347 AC XY: 47 AN XY: 135418

Gnomad AFR exome AF: 0.000309

Gnomad AMR exome AF: 0.000408

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000495

Gnomad OTH exome AF: 0.000656

GnomAD4 exome AF: 0.000438 AC: 639 AN: 1459418 Hom.: 2 Cov.: 29 AF XY: 0.000427 AC XY: 310 AN XY: 725990

Gnomad4 AFR exome AF: 0.000270

Gnomad4 AMR exome AF: 0.000471

Gnomad4 ASJ exome AF: 0.000115

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000512

Gnomad4 OTH exome AF: 0.000448

GnomAD4 genome AF: 0.000270 AC: 41 AN: 151740 Hom.: 0 Cov.: 32 AF XY: 0.000189 AC XY: 14 AN XY: 74116

Gnomad4 AFR AF: 0.000145

Gnomad4 AMR AF: 0.000330

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000413

Gnomad4 OTH AF: 0.000960

Alfa AF: 0.000519 Hom.: 0

Bravo AF: 0.000366

EpiCase AF: 0.000546

EpiControl AF: 0.000594

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

NEGR1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
Cadd	Benign	7.7
Dann	Benign	0.65

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: rs201170592; hg19: chr1-72163761; COSMIC: COSV60853267;