dbSNP rs4922847: NELL1:c.1981-82C>A (chr11-21570682-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006157.5(NELL1):c.1981-82C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.782 in 1,414,380 control chromosomes in the GnomAD database, including 443,168 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 0.67 ( 37386 hom., cov: 31)

Exomes 𝑓: 0.80 ( 405782 hom. )

Consequence

NELL1
NM_006157.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.10

Publications

5 publications found

Variant links:

Genes affected

NELL1 (HGNC:7750): (neural EGFL like 1) This gene encodes a cytoplasmic protein that contains epidermal growth factor (EGF)-like repeats. The encoded heterotrimeric protein may be involved in cell growth regulation and differentiation. A similar protein in rodents is involved in craniosynostosis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]

NELL1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.822 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006157.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NELL1	NM_006157.5	MANE Select	c.1981-82C>A	intron	N/A	NP_006148.2	Q92832-1
NELL1	NM_001288713.1		c.2065-82C>A	intron	N/A	NP_001275642.1	Q92832
NELL1	NM_201551.2		c.1840-82C>A	intron	N/A	NP_963845.1	Q92832-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NELL1	ENST00000357134.10	TSL:1 MANE Select	c.1981-82C>A	intron	N/A	ENSP00000349654.5	Q92832-1
NELL1	ENST00000532434.5	TSL:1	c.1840-82C>A	intron	N/A	ENSP00000437170.1	Q92832-2
NELL1	ENST00000298925.9	TSL:2	c.2065-82C>A	intron	N/A	ENSP00000298925.5	J3KNC5

Frequencies

GnomAD3 genomes

AF:

0.673

AC:

101965

AN:

151512

Hom.:

37383

Cov.:

show subpopulations

Gnomad AFR

AF:

0.368

Gnomad AMI

AF:

0.834

Gnomad AMR

AF:

0.684

Gnomad ASJ

AF:

0.846

Gnomad EAS

AF:

0.669

Gnomad SAS

AF:

0.610

Gnomad FIN

AF:

0.805

Gnomad MID

AF:

0.741

Gnomad NFE

AF:

0.828

Gnomad OTH

AF:

0.698

GnomAD4 exome

AF:

0.796

AC:

1004749

AN:

1262750

Hom.:

405782

AF XY:

0.793

AC XY:

496158

AN XY:

626018

show subpopulations

African (AFR)

AF:

0.354

AC:

10146

AN:

28642

American (AMR)

AF:

0.620

AC:

23325

AN:

37636

Ashkenazi Jewish (ASJ)

AF:

0.851

AC:

17704

AN:

20796

East Asian (EAS)

AF:

0.726

AC:

27295

AN:

37582

South Asian (SAS)

AF:

0.616

AC:

43646

AN:

70860

European-Finnish (FIN)

AF:

0.800

AC:

32799

AN:

41004

Middle Eastern (MID)

AF:

0.783

AC:

4004

AN:

5112

European-Non Finnish (NFE)

AF:

0.832

AC:

805379

AN:

967994

Other (OTH)

AF:

0.761

AC:

40451

AN:

53124

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

9145

18289

27434

36578

45723

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18044

36088

54132

72176

90220

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.673

AC:

101997

AN:

151630

Hom.:

37386

Cov.:

AF XY:

0.670

AC XY:

49633

AN XY:

74044

show subpopulations

African (AFR)

AF:

0.368

AC:

15243

AN:

41392

American (AMR)

AF:

0.683

AC:

10392

AN:

15210

Ashkenazi Jewish (ASJ)

AF:

0.846

AC:

2930

AN:

3464

East Asian (EAS)

AF:

0.669

AC:

3386

AN:

5064

South Asian (SAS)

AF:

0.613

AC:

2948

AN:

4810

European-Finnish (FIN)

AF:

0.805

AC:

8513

AN:

10570

Middle Eastern (MID)

AF:

0.731

AC:

215

AN:

294

European-Non Finnish (NFE)

AF:

0.828

AC:

56143

AN:

67808

Other (OTH)

AF:

0.696

AC:

1468

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1388

2775

4163

5550

6938

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

782

1564

2346

3128

3910

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.782

Hom.:

21231

Bravo

AF:

0.650

Asia WGS

AF:

0.588

AC:

2044

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.12

(source)

DANN

Benign

0.20

PhyloP100

-1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over