11-20847704-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_006157.5(NELL1):c.457G>A(p.Ala153Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00473 in 1,613,536 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0041 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0048 (30 hom.)
• Consequence: NELL1 NM_006157.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 6.74

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

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.010790795).
• BP6: Variant 11-20847704-G-A is Benign according to our data. Variant chr11-20847704-G-A is described in ClinVar as [Benign]. Clinvar id is 719361.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NELL1	NM_006157.5	c.457G>A	p.Ala153Thr	missense_variant	4/20	ENST00000357134.10
NELL1	NM_001288713.1	c.541G>A	p.Ala181Thr	missense_variant	5/21
NELL1	NM_201551.2	c.457G>A	p.Ala153Thr	missense_variant	4/19
NELL1	NM_001288714.1	c.336-37740G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NELL1	ENST00000357134.10	c.457G>A	p.Ala153Thr	missense_variant	4/20	1	NM_006157.5	P1

Frequencies

GnomAD3 genomes AF: 0.00411 AC: 625 AN: 152184 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.00111

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00223

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0174

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00520

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.00381 AC: 953 AN: 250384 Hom.: 4 AF XY: 0.00372 AC XY: 503 AN XY: 135282

Gnomad AFR exome AF: 0.00105

Gnomad AMR exome AF: 0.000959

Gnomad ASJ exome AF: 0.000199

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0166

Gnomad NFE exome AF: 0.00463

Gnomad OTH exome AF: 0.00311

GnomAD4 exome AF: 0.00480 AC: 7013 AN: 1461234 Hom.: 30 Cov.: 31 AF XY: 0.00453 AC XY: 3295 AN XY: 726880

Gnomad4 AFR exome AF: 0.000717

Gnomad4 AMR exome AF: 0.000896

Gnomad4 ASJ exome AF: 0.000268

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.0151

Gnomad4 NFE exome AF: 0.00536

Gnomad4 OTH exome AF: 0.00293

GnomAD4 genome AF: 0.00410 AC: 625 AN: 152302 Hom.: 3 Cov.: 33 AF XY: 0.00475 AC XY: 354 AN XY: 74466

Gnomad4 AFR AF: 0.00111

Gnomad4 AMR AF: 0.00222

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.0174

Gnomad4 NFE AF: 0.00520

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00421 Hom.: 0

Bravo AF: 0.00263

TwinsUK AF: 0.00458 AC: 17

ALSPAC AF: 0.00571 AC: 22

ESP6500AA AF: 0.00159 AC: 7

ESP6500EA AF: 0.00407 AC: 35

ExAC AF: 0.00358 AC: 435

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00442

EpiControl AF: 0.00464

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.33
Cadd	Uncertain	24
Dann	Pathogenic	1.0
DEOGEN2	Benign	0.031	T;T;.
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.88	D;D;D
MetaRNN	Benign	0.011	T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-2.3	N;N;N
REVEL	Benign	0.25
Sift	Uncertain	0.0030	D;D;D
Sift4G	Uncertain	0.0070	D;D;D
Polyphen		0.86, 0.98	.;P;D
Vest4		0.85
MVP		0.75
MPC		0.43
ClinPred		0.047	T
GERP RS		4.7
Varity_R		0.34
gMVP		0.69

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

Publications

LitVar

Other links and lift over

dbSNP: rs117839762; hg19: chr11-20869250; COSMIC: COSV104599777; COSMIC: COSV104599777;