1-71407536-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_173808.3(NEGR1):c.975C>T(p.Ser325=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00107 in 1,611,944 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0046 (5 hom., cov: 32)
  • Exomes 𝑓: 0.00070 (6 hom.)
• Consequence: NEGR1 NM_173808.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.174

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]

ZRANB2-DT (HGNC:43595): (ZRANB2 divergent transcript)

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 1-71407536-G-A is Benign according to our data. Variant chr1-71407536-G-A is described in ClinVar as [Benign]. Clinvar id is 775561.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.174 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEGR1	NM_173808.3	c.975C>T	p.Ser325=	synonymous_variant	7/7	ENST00000357731.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEGR1	ENST00000357731.10	c.975C>T	p.Ser325=	synonymous_variant	7/7	1	NM_173808.3	P1
ZRANB2-DT	ENST00000663294.1	n.383+5657G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00459 AC: 698 AN: 152038 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.0151

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00256

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.00431

GnomAD3 exomes AF: 0.00147 AC: 369 AN: 250468 Hom.: 0 AF XY: 0.00118 AC XY: 160 AN XY: 135488

Gnomad AFR exome AF: 0.0157

Gnomad AMR exome AF: 0.00160

Gnomad ASJ exome AF: 0.0000994

Gnomad EAS exome AF: 0.0000545

Gnomad SAS exome AF: 0.0000981

Gnomad FIN exome AF: 0.000462

Gnomad NFE exome AF: 0.000301

Gnomad OTH exome AF: 0.00180

GnomAD4 exome AF: 0.000697 AC: 1018 AN: 1459788 Hom.: 6 Cov.: 29 AF XY: 0.000661 AC XY: 480 AN XY: 726262

Gnomad4 AFR exome AF: 0.0152

Gnomad4 AMR exome AF: 0.00172

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000812

Gnomad4 FIN exome AF: 0.000393

Gnomad4 NFE exome AF: 0.000256

Gnomad4 OTH exome AF: 0.00169

GnomAD4 genome AF: 0.00461 AC: 702 AN: 152156 Hom.: 5 Cov.: 32 AF XY: 0.00460 AC XY: 342 AN XY: 74386

Gnomad4 AFR AF: 0.0151

Gnomad4 AMR AF: 0.00256

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.0000943

Gnomad4 NFE AF: 0.000309

Gnomad4 OTH AF: 0.00427

Alfa AF: 0.00295 Hom.: 2

Bravo AF: 0.00536

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.000328

EpiControl AF: 0.000297

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	-0.48
Cadd	Benign	6.8
Dann	Benign	0.83

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs144477627; hg19: chr1-71873219;