11-21404866-G-A

Variant names:

• chr11-21404866-G-A
• rs1981410
• NM_006157.5:c.1645+33918G>A

Variant summary

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

The NM_006157.5(NELL1):​c.1645+33918G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 151,840 control chromosomes in the GnomAD database, including 13,456 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 0.41 (13456 hom., cov: 32)
• Consequence: NELL1 NM_006157.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0900
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.503 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NELL1	NM_006157.5	MANE Select	c.1645+33918G>A		intron	N/A	NP_006148.2	Q92832-1
	NELL1	NM_001288713.1		c.1729+33918G>A		intron	N/A	NP_001275642.1	Q92832
	NELL1	NM_201551.2		c.1645+33918G>A		intron	N/A	NP_963845.1	Q92832-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NELL1	ENST00000357134.10	TSL:1 MANE Select	c.1645+33918G>A		intron	N/A	ENSP00000349654.5	Q92832-1
	NELL1	ENST00000532434.5	TSL:1	c.1645+33918G>A		intron	N/A	ENSP00000437170.1	Q92832-2
	NELL1	ENST00000534263.1	TSL:1	n.923+33918G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.411 AC: 62323 AN: 151722 Hom.: 13442 Cov.: 32

Gnomad AFR AF: 0.509

Gnomad AMI AF: 0.621

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.495

Gnomad EAS AF: 0.0797

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.375

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.423

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

GnomAD4 genome AF: 0.411 AC: 62379 AN: 151840 Hom.: 13456 Cov.: 32 AF XY: 0.404 AC XY: 29972 AN XY: 74184

African (AFR) AF: 0.509 AC: 21090 AN: 41432

American (AMR) AF: 0.350 AC: 5347 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.495 AC: 1713 AN: 3464

East Asian (EAS) AF: 0.0798 AC: 408 AN: 5110

South Asian (SAS) AF: 0.348 AC: 1676 AN: 4816

European-Finnish (FIN) AF: 0.375 AC: 3966 AN: 10562

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.392 AC: 26578 AN: 67874

Other (OTH) AF: 0.419 AC: 885 AN: 2110

Alfa AF: 0.393 Hom.: 19817

Bravo AF: 0.414

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.13
DANN	Benign	0.38
PhyloP100		-0.090
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: rs1981410; hg19: chr11-21426412;