chr1-71754638-C-A

Variant names:

• chr1-71754638-C-A
• rs6671557
• NM_173808.3:c.535+21534G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173808.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEGR1	NM_173808.3	MANE Select	c.535+21534G>T		intron	N/A	NP_776169.2	Q7Z3B1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEGR1	ENST00000357731.10	TSL:1 MANE Select	c.535+21534G>T		intron	N/A	ENSP00000350364.4	Q7Z3B1-1
	NEGR1	ENST00000306821.3	TSL:1	c.151+21534G>T		intron	N/A	ENSP00000305938.3	Q7Z3B1-2
	NEGR1	ENST00000467479.1	TSL:5	n.532+21534G>T		intron	N/A

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

African (AFR) AF: 0.0121 AC: 501 AN: 41496

American (AMR) AF: 0.0528 AC: 806 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.0432 AC: 150 AN: 3470

East Asian (EAS) AF: 0.134 AC: 684 AN: 5118

South Asian (SAS) AF: 0.102 AC: 488 AN: 4804

European-Finnish (FIN) AF: 0.0652 AC: 690 AN: 10580

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0471 AC: 3205 AN: 68000

Other (OTH) AF: 0.0355 AC: 75 AN: 2110

Alfa AF: 0.0426 Hom.: 83

Bravo AF: 0.0415

Asia WGS AF: 0.0800 AC: 278 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.19
DANN	Benign	0.84
PhyloP100		-0.80
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6671557; hg19: chr1-72220321;