chr11-21245872-A-G

Variant names:

• chr11-21245872-A-G
• rs1670646
• NM_006157.5:c.1549+16418A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006157.5(NELL1):​c.1549+16418A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.52 in 151,994 control chromosomes in the GnomAD database, including 21,056 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 0.52 (21056 hom., cov: 32)
• Consequence: NELL1 NM_006157.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0720
• Publications: 1 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.557 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NELL1	NM_006157.5	MANE Select	c.1549+16418A>G		intron	N/A	NP_006148.2
	NELL1	NM_001288713.1		c.1633+16418A>G		intron	N/A	NP_001275642.1
	NELL1	NM_201551.2		c.1549+16418A>G		intron	N/A	NP_963845.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NELL1	ENST00000357134.10	TSL:1 MANE Select	c.1549+16418A>G		intron	N/A	ENSP00000349654.5
	NELL1	ENST00000532434.5	TSL:1	c.1549+16418A>G		intron	N/A	ENSP00000437170.1
	NELL1	ENST00000298925.9	TSL:2	c.1633+16418A>G		intron	N/A	ENSP00000298925.5

Frequencies

GnomAD3 genomes AF: 0.520 AC: 78992 AN: 151878 Hom.: 21032 Cov.: 32

Gnomad AFR AF: 0.552

Gnomad AMI AF: 0.567

Gnomad AMR AF: 0.420

Gnomad ASJ AF: 0.594

Gnomad EAS AF: 0.439

Gnomad SAS AF: 0.275

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.562

Gnomad OTH AF: 0.524

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

GnomAD4 genome AF: 0.520 AC: 79051 AN: 151994 Hom.: 21056 Cov.: 32 AF XY: 0.508 AC XY: 37754 AN XY: 74292

African (AFR) AF: 0.552 AC: 22900 AN: 41462

American (AMR) AF: 0.420 AC: 6401 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.594 AC: 2062 AN: 3470

East Asian (EAS) AF: 0.438 AC: 2259 AN: 5156

South Asian (SAS) AF: 0.274 AC: 1322 AN: 4824

European-Finnish (FIN) AF: 0.392 AC: 4145 AN: 10570

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.562 AC: 38198 AN: 67944

Other (OTH) AF: 0.522 AC: 1102 AN: 2110

Alfa AF: 0.547 Hom.: 45238

Bravo AF: 0.526

Asia WGS AF: 0.366 AC: 1274 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.8
DANN	Benign	0.77
PhyloP100		-0.072
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: rs1670646; hg19: chr11-21267418;