NM_032442.3:c.4252A>G

Variant names:

• chr17-7317527-T-C
• rs144766007
• NM_032442.3:c.4252A>G

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_032442.3(NEURL4):​c.4252A>G​(p.Met1418Val) variant causes a missense change. The variant allele was found at a frequency of 0.00672 in 1,614,164 control chromosomes in the GnomAD database, including 75 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0046 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0069 (72 hom.)
• Consequence: NEURL4 NM_032442.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.17
• Publications: 9 publications found

Genes affected

NEURL4 (HGNC:34410): (neuralized E3 ubiquitin protein ligase 4) The protein encoded by this gene is predicted and it includes two isoforms resulting from two alternatively spliced transcript variants. [provided by RefSeq, Jul 2008]

ENSG00000261915 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0062610805).
• BP6: Variant 17-7317527-T-C is Benign according to our data. Variant chr17-7317527-T-C is described in ClinVar as [Benign]. Clinvar id is 771020.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEURL4	NM_032442.3	c.4252A>G	p.Met1418Val	missense_variant	Exon 27 of 29	ENST00000399464.7	NP_115818.2
NEURL4	NM_001005408.2	c.4246A>G	p.Met1416Val	missense_variant	Exon 27 of 29		NP_001005408.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEURL4	ENST00000399464.7	c.4252A>G	p.Met1418Val	missense_variant	Exon 27 of 29	1	NM_032442.3	ENSP00000382390.2
ENSG00000261915	ENST00000575474.1	n.691A>G		non_coding_transcript_exon_variant	Exon 6 of 19	5		ENSP00000468772.1

Frequencies

GnomAD3 genomes AF: 0.00458 AC: 697 AN: 152180 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.00147

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00563

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0104

Gnomad FIN AF: 0.000376

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00703

Gnomad OTH AF: 0.00574

GnomAD2 exomes AF: 0.00518 AC: 1292 AN: 249564 AF XY: 0.00564

Gnomad AFR exome AF: 0.00116

Gnomad AMR exome AF: 0.00278

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000556

Gnomad FIN exome AF: 0.000186

Gnomad NFE exome AF: 0.00603

Gnomad OTH exome AF: 0.00478

GnomAD4 exome AF: 0.00694 AC: 10146 AN: 1461866 Hom.: 72 Cov.: 33 AF XY: 0.00709 AC XY: 5156 AN XY: 727238

African (AFR) AF: 0.000926 AC: 31 AN: 33480

American (AMR) AF: 0.00293 AC: 131 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.0137 AC: 1182 AN: 86258

European-Finnish (FIN) AF: 0.000393 AC: 21 AN: 53420

Middle Eastern (MID) AF: 0.00416 AC: 24 AN: 5768

European-Non Finnish (NFE) AF: 0.00755 AC: 8396 AN: 1111988

Other (OTH) AF: 0.00594 AC: 359 AN: 60396

GnomAD4 genome AF: 0.00456 AC: 695 AN: 152298 Hom.: 3 Cov.: 33 AF XY: 0.00442 AC XY: 329 AN XY: 74472

African (AFR) AF: 0.00147 AC: 61 AN: 41558

American (AMR) AF: 0.00562 AC: 86 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00995 AC: 48 AN: 4822

European-Finnish (FIN) AF: 0.000376 AC: 4 AN: 10628

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00703 AC: 478 AN: 68008

Other (OTH) AF: 0.00568 AC: 12 AN: 2114

Alfa AF: 0.00568 Hom.: 8

Bravo AF: 0.00474

TwinsUK AF: 0.00782 AC: 29

ALSPAC AF: 0.00830 AC: 32

ESP6500AA AF: 0.000733 AC: 3

ESP6500EA AF: 0.00835 AC: 70

ExAC AF: 0.00526 AC: 636

Asia WGS AF: 0.00635 AC: 22 AN: 3478

EpiCase AF: 0.00583

EpiControl AF: 0.00682

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jan 26, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	22
DANN	Benign	0.83
DEOGEN2	Benign	0.0059	.;T;.
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.32
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.82	T;T;T
MetaRNN	Benign	0.0063	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.050	.;N;.
PhyloP100		4.2
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	0.49	N;N;.
REVEL	Benign	0.074
Sift	Benign	1.0	T;T;.
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0	B;B;.
Vest4		0.39
MVP		0.043
MPC		0.54
ClinPred		0.0074	T
GERP RS		3.8
Varity_R		0.13
gMVP		0.57
Mutation Taster		=94/6	polymorphism

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: rs144766007; hg19: chr17-7220846; COSMIC: COSV59747908;