rs4675310

Positions:

• chr2-203016111-G-A
• chr2-203016111-G-C
• chr2-203016111-G-T

Variant summary

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

The NM_001378026.1(NBEAL1):​c.-229-45G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.897 in 289,716 control chromosomes in the GnomAD database, including 116,849 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 0.90 (62319 hom., cov: 33)
  • Exomes 𝑓: 0.89 (54530 hom.)
• Consequence: NBEAL1 NM_001378026.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21

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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.963 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NBEAL1	NM_001378026.1	c.-229-45G>A		intron_variant		ENST00000683969.1	NP_001364955.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NBEAL1	ENST00000683969.1	c.-229-45G>A		intron_variant			NM_001378026.1	ENSP00000508055	P4

Frequencies

GnomAD3 genomes AF: 0.904 AC: 137575 AN: 152190 Hom.: 62269 Cov.: 33

Gnomad AFR AF: 0.944

Gnomad AMI AF: 0.796

Gnomad AMR AF: 0.898

Gnomad ASJ AF: 0.889

Gnomad EAS AF: 0.985

Gnomad SAS AF: 0.969

Gnomad FIN AF: 0.894

Gnomad MID AF: 0.896

Gnomad NFE AF: 0.875

Gnomad OTH AF: 0.867

GnomAD4 exome AF: 0.890 AC: 122305 AN: 137408 Hom.: 54530 Cov.: 0 AF XY: 0.890 AC XY: 62764 AN XY: 70534

Gnomad4 AFR exome AF: 0.949

Gnomad4 AMR exome AF: 0.899

Gnomad4 ASJ exome AF: 0.892

Gnomad4 EAS exome AF: 0.991

Gnomad4 SAS exome AF: 0.969

Gnomad4 FIN exome AF: 0.889

Gnomad4 NFE exome AF: 0.872

Gnomad4 OTH exome AF: 0.889

GnomAD4 genome AF: 0.904 AC: 137679 AN: 152308 Hom.: 62319 Cov.: 33 AF XY: 0.907 AC XY: 67579 AN XY: 74472

Gnomad4 AFR AF: 0.944

Gnomad4 AMR AF: 0.898

Gnomad4 ASJ AF: 0.889

Gnomad4 EAS AF: 0.985

Gnomad4 SAS AF: 0.968

Gnomad4 FIN AF: 0.894

Gnomad4 NFE AF: 0.875

Gnomad4 OTH AF: 0.860

Alfa AF: 0.876 Hom.: 59044

Bravo AF: 0.904

Asia WGS AF: 0.958 AC: 3334 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.0
DANN	Benign	0.50

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: rs4675310; hg19: chr2-203880834;