chr11-20885476-C-T

Variant names:

• chr11-20885476-C-T
• rs1201441915
• NM_006157.5:c.539C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_006157.5(NELL1):​c.539C>T​(p.Thr180Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,613,176 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: NELL1 NM_006157.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.04
• Publications: 0 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]

LOC105376585 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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.539C>T	p.Thr180Ile	missense	Exon 5 of 20	NP_006148.2	Q92832-1
	NELL1	NM_001288713.1		c.623C>T	p.Thr208Ile	missense	Exon 6 of 21	NP_001275642.1	Q92832
	NELL1	NM_201551.2		c.539C>T	p.Thr180Ile	missense	Exon 5 of 19	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.539C>T	p.Thr180Ile	missense	Exon 5 of 20	ENSP00000349654.5	Q92832-1
	NELL1	ENST00000532434.5	TSL:1	c.539C>T	p.Thr180Ile	missense	Exon 5 of 19	ENSP00000437170.1	Q92832-2
	NELL1	ENST00000298925.9	TSL:2	c.623C>T	p.Thr208Ile	missense	Exon 6 of 21	ENSP00000298925.5	J3KNC5

Frequencies

GnomAD3 genomes AF: 0.0000591 AC: 9 AN: 152194 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000517 AC: 13 AN: 251420 AF XY: 0.0000589

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000376

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000144 AC: 21 AN: 1460982 Hom.: 0 Cov.: 29 AF XY: 0.0000165 AC XY: 12 AN XY: 726876

African (AFR) AF: 0.00 AC: 0 AN: 33444

American (AMR) AF: 0.000447 AC: 20 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111204

Other (OTH) AF: 0.00 AC: 0 AN: 60370

GnomAD4 genome AF: 0.0000591 AC: 9 AN: 152194 Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6 AN XY: 74336

African (AFR) AF: 0.00 AC: 0 AN: 41440

American (AMR) AF: 0.000589 AC: 9 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68046

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000907

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.035	T
Eigen	Benign	0.077
Eigen_PC	Benign	0.088
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.064	D
MetaRNN	Uncertain	0.47	T
MetaSVM	Uncertain	0.26	D
MutationAssessor	Uncertain	2.3	M
PhyloP100		2.0
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-2.0	N
REVEL	Uncertain	0.41
Sift	Uncertain	0.016	D
Sift4G	Benign	0.31	T
Polyphen		0.28	B
Vest4		0.67
MutPred		0.42		Loss of catalytic residue at T180 (P = 0.0132)
MVP		0.81
MPC		0.094
ClinPred		0.21	T
GERP RS		4.6
Varity_R		0.18
gMVP		0.28
Mutation Taster		=77/23	polymorphism

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: rs1201441915; hg19: chr11-20907022; COSMIC: COSV54340301;