NM_032442.3:c.4257A>C

Variant names:

• chr17-7317522-T-G
• rs75583706
• NM_032442.3:c.4257A>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_032442.3(NEURL4):​c.4257A>C​(p.Ala1419Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0045 in 1,614,160 control chromosomes in the GnomAD database, including 307 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.024 (150 hom., cov: 32)
  • Exomes 𝑓: 0.0025 (157 hom.)
• Consequence: NEURL4 NM_032442.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.91
• Publications: 3 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 17-7317522-T-G is Benign according to our data. Variant chr17-7317522-T-G is described in ClinVar as Benign. ClinVar VariationId is 714725.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.91 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0807 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032442.3. 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
	NEURL4	NM_032442.3	MANE Select	c.4257A>C	p.Ala1419Ala	synonymous	Exon 27 of 29	NP_115818.2	Q96JN8-1
	NEURL4	NM_001005408.2		c.4251A>C	p.Ala1417Ala	synonymous	Exon 27 of 29	NP_001005408.1	Q96JN8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEURL4	ENST00000399464.7	TSL:1 MANE Select	c.4257A>C	p.Ala1419Ala	synonymous	Exon 27 of 29	ENSP00000382390.2	Q96JN8-1
	NEURL4	ENST00000315614.11	TSL:1	c.4251A>C	p.Ala1417Ala	synonymous	Exon 27 of 29	ENSP00000319826.7	Q96JN8-2
	ENSG00000261915	ENST00000575474.1	TSL:5	n.696A>C		non_coding_transcript_exon	Exon 6 of 19	ENSP00000468772.1	K7ESM1

Frequencies

GnomAD3 genomes AF: 0.0237 AC: 3604 AN: 152156 Hom.: 150 Cov.: 32

Gnomad AFR AF: 0.0832

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00759

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.0124

GnomAD2 exomes AF: 0.00627 AC: 1565 AN: 249566 AF XY: 0.00492

Gnomad AFR exome AF: 0.0903

Gnomad AMR exome AF: 0.00368

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000238

Gnomad OTH exome AF: 0.00165

GnomAD4 exome AF: 0.00250 AC: 3652 AN: 1461886 Hom.: 157 Cov.: 33 AF XY: 0.00212 AC XY: 1541 AN XY: 727246

African (AFR) AF: 0.0910 AC: 3046 AN: 33476

American (AMR) AF: 0.00398 AC: 178 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

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

South Asian (SAS) AF: 0.000116 AC: 10 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

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

European-Non Finnish (NFE) AF: 0.0000890 AC: 99 AN: 1112012

Other (OTH) AF: 0.00488 AC: 295 AN: 60394

GnomAD4 genome AF: 0.0237 AC: 3606 AN: 152274 Hom.: 150 Cov.: 32 AF XY: 0.0227 AC XY: 1691 AN XY: 74452

African (AFR) AF: 0.0830 AC: 3446 AN: 41526

American (AMR) AF: 0.00758 AC: 116 AN: 15302

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 68020

Other (OTH) AF: 0.0123 AC: 26 AN: 2116

Alfa AF: 0.0124 Hom.: 43

Bravo AF: 0.0274

Asia WGS AF: 0.00433 AC: 16 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000356

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.72
DANN	Benign	0.64
PhyloP100		-1.9
Mutation Taster		=98/2	polymorphism (auto)

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: rs75583706; hg19: chr17-7220841;