2-203017870-A-C

Position:

• chr2-203017870-A-C

Variant summary

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

The NM_001378026.1(NBEAL1):​c.51+1435A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 151,906 control chromosomes in the GnomAD database, including 16,212 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 0.43 (16212 hom., cov: 31)
• Consequence: NBEAL1 NM_001378026.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.223

Genes affected

NBEAL1 (HGNC:20681): (neurobeachin like 1) Predicted to enable protein kinase binding activity. Predicted to be involved in protein localization. Predicted to be active in cytosol and membrane. [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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NBEAL1	NM_001378026.1	c.51+1435A>C		intron_variant		ENST00000683969.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NBEAL1	ENST00000683969.1	c.51+1435A>C		intron_variant			NM_001378026.1	P4

Frequencies

GnomAD3 genomes AF: 0.427 AC: 64856 AN: 151788 Hom.: 16224 Cov.: 31

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.640

Gnomad AMR AF: 0.448

Gnomad ASJ AF: 0.696

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.601

Gnomad FIN AF: 0.424

Gnomad MID AF: 0.685

Gnomad NFE AF: 0.557

Gnomad OTH AF: 0.472

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.427 AC: 64830 AN: 151906 Hom.: 16212 Cov.: 31 AF XY: 0.426 AC XY: 31637 AN XY: 74220

Gnomad4 AFR AF: 0.171

Gnomad4 AMR AF: 0.447

Gnomad4 ASJ AF: 0.696

Gnomad4 EAS AF: 0.305

Gnomad4 SAS AF: 0.600

Gnomad4 FIN AF: 0.424

Gnomad4 NFE AF: 0.557

Gnomad4 OTH AF: 0.467

Alfa AF: 0.544 Hom.: 35445

Bravo AF: 0.410

Asia WGS AF: 0.432 AC: 1495 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.0
DANN	Benign	0.74

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: rs1947983; hg19: chr2-203882593;