1-71611112-G-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_173808.3(NEGR1):c.702C>A(p.Thr234=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00237 in 1,613,614 control chromosomes in the GnomAD database, including 103 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.013 (55 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (48 hom.)
• Consequence: NEGR1 NM_173808.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.76

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 1-71611112-G-T is Benign according to our data. Variant chr1-71611112-G-T is described in ClinVar as [Benign]. Clinvar id is 767678.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.76 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0128 (1942/152052) while in subpopulation AFR AF= 0.0444 (1841/41466). AF 95% confidence interval is 0.0427. There are 55 homozygotes in gnomad4. There are 905 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 55 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEGR1	NM_173808.3	c.702C>A	p.Thr234=	synonymous_variant	5/7	ENST00000357731.10
NEGR1	XM_011541200.4	c.702C>A	p.Thr234=	synonymous_variant	5/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEGR1	ENST00000357731.10	c.702C>A	p.Thr234=	synonymous_variant	5/7	1	NM_173808.3	P1
NEGR1	ENST00000306821.3	c.318C>A	p.Thr106=	synonymous_variant	5/7	1

Frequencies

GnomAD3 genomes AF: 0.0127 AC: 1932 AN: 151934 Hom.: 55 Cov.: 32

Gnomad AFR AF: 0.0443

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00406

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000623

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.0125

GnomAD3 exomes AF: 0.00318 AC: 799 AN: 251236 Hom.: 16 AF XY: 0.00213 AC XY: 289 AN XY: 135858

Gnomad AFR exome AF: 0.0430

Gnomad AMR exome AF: 0.00202

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000114

Gnomad OTH exome AF: 0.00244

GnomAD4 exome AF: 0.00129 AC: 1889 AN: 1461562 Hom.: 48 Cov.: 30 AF XY: 0.00111 AC XY: 806 AN XY: 727110

Gnomad4 AFR exome AF: 0.0442

Gnomad4 AMR exome AF: 0.00224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000696

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000115

Gnomad4 OTH exome AF: 0.00267

GnomAD4 genome AF: 0.0128 AC: 1942 AN: 152052 Hom.: 55 Cov.: 32 AF XY: 0.0122 AC XY: 905 AN XY: 74342

Gnomad4 AFR AF: 0.0444

Gnomad4 AMR AF: 0.00406

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000624

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000147

Gnomad4 OTH AF: 0.0124

Alfa AF: 0.00494 Hom.: 7

Bravo AF: 0.0139

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.11
Dann	Benign	0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs61729931; hg19: chr1-72076795;