11-21372313-C-T

Variant names:

• chr11-21372313-C-T
• rs7120820
• NM_006157.5:c.1645+1365C>T

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+1365C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 151,464 control chromosomes in the GnomAD database, including 10,093 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 0.36 (10093 hom., cov: 31)
• Consequence: NELL1 NM_006157.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.42
• Publications: 2 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 (AMR) allele frequency at 95% confidence interval = 0.511 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+1365C>T		intron	N/A	NP_006148.2	Q92832-1
	NELL1	NM_001288713.1		c.1729+1365C>T		intron	N/A	NP_001275642.1	Q92832
	NELL1	NM_201551.2		c.1645+1365C>T		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+1365C>T		intron	N/A	ENSP00000349654.5	Q92832-1
	NELL1	ENST00000532434.5	TSL:1	c.1645+1365C>T		intron	N/A	ENSP00000437170.1	Q92832-2
	NELL1	ENST00000534263.1	TSL:1	n.923+1365C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.359 AC: 54268 AN: 151354 Hom.: 10081 Cov.: 31

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.520

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.309

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.361

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

GnomAD4 genome AF: 0.359 AC: 54306 AN: 151464 Hom.: 10093 Cov.: 31 AF XY: 0.358 AC XY: 26445 AN XY: 73956

African (AFR) AF: 0.291 AC: 12022 AN: 41352

American (AMR) AF: 0.521 AC: 7907 AN: 15178

Ashkenazi Jewish (ASJ) AF: 0.320 AC: 1110 AN: 3466

East Asian (EAS) AF: 0.394 AC: 2020 AN: 5128

South Asian (SAS) AF: 0.300 AC: 1441 AN: 4806

European-Finnish (FIN) AF: 0.309 AC: 3235 AN: 10458

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.375 AC: 25383 AN: 67776

Other (OTH) AF: 0.358 AC: 750 AN: 2096

Alfa AF: 0.371 Hom.: 26441

Bravo AF: 0.375

Asia WGS AF: 0.338 AC: 1167 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.065
DANN	Benign	0.19
PhyloP100		-2.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7120820; hg19: chr11-21393859;