17-7316233-C-T

Variant names:

• chr17-7316233-C-T
• rs201366443
• NM_032442.3:c.4579G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_032442.3(NEURL4):​c.4579G>A​(p.Ala1527Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000656 in 1,613,772 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00091 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00063 (3 hom.)
• Consequence: NEURL4 NM_032442.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.705
• Publications: 2 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0034599602).
• BP6: Variant 17-7316233-C-T is Benign according to our data. Variant chr17-7316233-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3390331.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEURL4	NM_032442.3	c.4579G>A	p.Ala1527Thr	missense_variant	Exon 29 of 29	ENST00000399464.7	NP_115818.2
NEURL4	NM_001005408.2	c.4573G>A	p.Ala1525Thr	missense_variant	Exon 29 of 29		NP_001005408.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEURL4	ENST00000399464.7	c.4579G>A	p.Ala1527Thr	missense_variant	Exon 29 of 29	1	NM_032442.3	ENSP00000382390.2
ENSG00000261915	ENST00000575474.1	n.975+43G>A		intron_variant	Intron 8 of 18	5		ENSP00000468772.1

Frequencies

GnomAD3 genomes AF: 0.000914 AC: 139 AN: 152138 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00971

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000456

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.00114 AC: 284 AN: 249484 AF XY: 0.00116

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00119

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00951

Gnomad NFE exome AF: 0.000512

Gnomad OTH exome AF: 0.000825

GnomAD4 exome AF: 0.000629 AC: 919 AN: 1461516 Hom.: 3 Cov.: 31 AF XY: 0.000612 AC XY: 445 AN XY: 727050

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.0000447 AC: 2 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000727 AC: 19 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000104 AC: 9 AN: 86244

European-Finnish (FIN) AF: 0.00871 AC: 465 AN: 53414

Middle Eastern (MID) AF: 0.000882 AC: 5 AN: 5670

European-Non Finnish (NFE) AF: 0.000347 AC: 386 AN: 1111786

Other (OTH) AF: 0.000547 AC: 33 AN: 60372

GnomAD4 genome AF: 0.000913 AC: 139 AN: 152256 Hom.: 1 Cov.: 32 AF XY: 0.00138 AC XY: 103 AN XY: 74448

African (AFR) AF: 0.00 AC: 0 AN: 41540

American (AMR) AF: 0.00 AC: 0 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.000577 AC: 2 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00971 AC: 103 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000456 AC: 31 AN: 68006

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.000475 Hom.: 0

Bravo AF: 0.000185

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000481 AC: 4

ExAC AF: 0.000976 AC: 118

EpiCase AF: 0.000763

EpiControl AF: 0.000474

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Oct 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

NEURL4: BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0085	.;T;.
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.067	N
LIST_S2	Benign	0.75	T;T;T
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.0035	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.89	.;L;.
PhyloP100		0.70
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.90	N;N;.
REVEL	Benign	0.036
Sift	Benign	0.21	T;T;.
Sift4G	Benign	0.30	T;T;T
Polyphen		0.0070	B;B;.
Vest4		0.042
MVP		0.043
MPC		0.51
ClinPred		0.023	T
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.082
gMVP		0.23
Mutation Taster		=100/0	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: rs201366443; hg19: chr17-7219552;