rs6671557

chr1-71754638-C-Achr1-71754638-C-Gchr1-71754638-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173808.3(NEGR1):c.535+21534G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0438 in 152,038 control chromosomes in the GnomAD database, including 211 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 0.044 (211 hom., cov: 31)
• Consequence: NEGR1 NM_173808.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.799

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEGR1	NM_173808.3	c.535+21534G>T		intron_variant		ENST00000357731.10
NEGR1	XM_011541200.4	c.535+21534G>T		intron_variant
NEGR1	XM_011541201.4	c.535+21534G>T		intron_variant
NEGR1	XM_017000961.3	c.535+21534G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEGR1	ENST00000357731.10	c.535+21534G>T		intron_variant		1	NM_173808.3	P1
NEGR1	ENST00000306821.3	c.151+21534G>T		intron_variant		1
NEGR1	ENST00000467479.1	n.532+21534G>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0438 AC: 6657 AN: 151918 Hom.: 212 Cov.: 31

Gnomad AFR AF: 0.0121

Gnomad AMI AF: 0.0571

Gnomad AMR AF: 0.0523

Gnomad ASJ AF: 0.0432

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.0652

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0471

Gnomad OTH AF: 0.0364

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

GnomAD4 genome AF: 0.0438 AC: 6660 AN: 152038 Hom.: 211 Cov.: 31 AF XY: 0.0461 AC XY: 3428 AN XY: 74296

Gnomad4 AFR AF: 0.0121

Gnomad4 AMR AF: 0.0528

Gnomad4 ASJ AF: 0.0432

Gnomad4 EAS AF: 0.134

Gnomad4 SAS AF: 0.102

Gnomad4 FIN AF: 0.0652

Gnomad4 NFE AF: 0.0471

Gnomad4 OTH AF: 0.0355

Alfa AF: 0.0417 Hom.: 74

Bravo AF: 0.0415

Asia WGS AF: 0.0800 AC: 278 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	0.19
Dann	Benign	0.84

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: rs6671557; hg19: chr1-72220321;