5-172686071-G-A

Position:

• chr5-172686071-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001142651.3(NEURL1B):​c.1298-100G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 1,418,122 control chromosomes in the GnomAD database, including 11,612 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.17 (3016 hom., cov: 32)
  • Exomes 𝑓: 0.11 (8596 hom.)
• Consequence: NEURL1B NM_001142651.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.47

Genes affected

NEURL1B (HGNC:35422): (neuralized E3 ubiquitin protein ligase 1B) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in ubiquitin-dependent endocytosis. Located in actin cytoskeleton and cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEURL1B	NM_001142651.3	c.1298-100G>A		intron_variant		ENST00000369800.6	NP_001136123.1
NEURL1B	NM_001308177.2	c.752-100G>A		intron_variant			NP_001295106.1
NEURL1B	NM_001308178.2	c.578-100G>A		intron_variant			NP_001295107.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEURL1B	ENST00000369800.6	c.1298-100G>A		intron_variant		1	NM_001142651.3	ENSP00000358815.5
NEURL1B	ENST00000522853.5	c.752-100G>A		intron_variant		1		ENSP00000430001.1
NEURL1B	ENST00000520919.5	c.578-100G>A		intron_variant		1		ENSP00000429797.1

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26542 AN: 152030 Hom.: 2999 Cov.: 32

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.0620

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0999

Gnomad OTH AF: 0.153

GnomAD4 exome AF: 0.107 AC: 135607 AN: 1265974 Hom.: 8596 AF XY: 0.106 AC XY: 65951 AN XY: 622170

Gnomad4 AFR exome AF: 0.327

Gnomad4 AMR exome AF: 0.222

Gnomad4 ASJ exome AF: 0.0605

Gnomad4 EAS exome AF: 0.134

Gnomad4 SAS exome AF: 0.0972

Gnomad4 FIN exome AF: 0.132

Gnomad4 NFE exome AF: 0.0965

Gnomad4 OTH exome AF: 0.116

GnomAD4 genome AF: 0.175 AC: 26608 AN: 152148 Hom.: 3016 Cov.: 32 AF XY: 0.176 AC XY: 13108 AN XY: 74378

Gnomad4 AFR AF: 0.321

Gnomad4 AMR AF: 0.194

Gnomad4 ASJ AF: 0.0620

Gnomad4 EAS AF: 0.179

Gnomad4 SAS AF: 0.0994

Gnomad4 FIN AF: 0.139

Gnomad4 NFE AF: 0.100

Gnomad4 OTH AF: 0.152

Alfa AF: 0.0951 Hom.: 388

Bravo AF: 0.189

Asia WGS AF: 0.145 AC: 504 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.011
DANN	Benign	0.47

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

Publications

LitVar

Other links and lift over

dbSNP: rs17075071; hg19: chr5-172113074;