rs2056206

Positions:

• chr1-71471227-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.941-63657A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.494 in 152,040 control chromosomes in the GnomAD database, including 18,766 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 0.49 (18766 hom., cov: 33)
• Consequence: NEGR1 NM_173808.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.194

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.541 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEGR1	NM_173808.3	c.941-63657A>G		intron_variant		ENST00000357731.10	NP_776169.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEGR1	ENST00000357731.10	c.941-63657A>G		intron_variant		1	NM_173808.3	ENSP00000350364	P1
ZRANB2-DT	ENST00000663294.1	n.384-15171T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.494 AC: 75023 AN: 151922 Hom.: 18744 Cov.: 33

Gnomad AFR AF: 0.437

Gnomad AMI AF: 0.622

Gnomad AMR AF: 0.511

Gnomad ASJ AF: 0.503

Gnomad EAS AF: 0.384

Gnomad SAS AF: 0.559

Gnomad FIN AF: 0.588

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.512

Gnomad OTH AF: 0.484

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

GnomAD4 genome AF: 0.494 AC: 75091 AN: 152040 Hom.: 18766 Cov.: 33 AF XY: 0.496 AC XY: 36888 AN XY: 74306

Gnomad4 AFR AF: 0.437

Gnomad4 AMR AF: 0.511

Gnomad4 ASJ AF: 0.503

Gnomad4 EAS AF: 0.385

Gnomad4 SAS AF: 0.559

Gnomad4 FIN AF: 0.588

Gnomad4 NFE AF: 0.512

Gnomad4 OTH AF: 0.490

Alfa AF: 0.495 Hom.: 5524

Bravo AF: 0.480

Asia WGS AF: 0.505 AC: 1759 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	9.8
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: rs2056206; hg19: chr1-71936910;