chr2-203057352-A-G

Position:

• chr2-203057352-A-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001378026.1(NBEAL1):​c.414A>G​(p.Glu138Glu) variant causes a synonymous change. The variant allele was found at a frequency of 0.00724 in 1,550,320 control chromosomes in the GnomAD database, including 63 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0049 (5 hom., cov: 33)
  • Exomes 𝑓: 0.0075 (58 hom.)
• Consequence: NBEAL1 NM_001378026.1 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 4.54

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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 2-203057352-A-G is Benign according to our data. Variant chr2-203057352-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 714942.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NBEAL1	NM_001378026.1	c.414A>G	p.Glu138Glu	synonymous_variant	6/56	ENST00000683969.1	NP_001364955.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NBEAL1	ENST00000683969.1	c.414A>G	p.Glu138Glu	synonymous_variant	6/56		NM_001378026.1	ENSP00000508055.1

Frequencies

GnomAD3 genomes AF: 0.00491 AC: 747 AN: 152224 Hom.: 5 Cov.: 33

Gnomad AFR AF: 0.00109

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00151

Gnomad ASJ AF: 0.00548

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00660

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00847

Gnomad OTH AF: 0.00526

GnomAD3 exomes AF: 0.00477 AC: 751 AN: 157324 Hom.: 4 AF XY: 0.00463 AC XY: 386 AN XY: 83408

Gnomad AFR exome AF: 0.000494

Gnomad AMR exome AF: 0.00110

Gnomad ASJ exome AF: 0.00647

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000484

Gnomad FIN exome AF: 0.00697

Gnomad NFE exome AF: 0.00842

Gnomad OTH exome AF: 0.00546

GnomAD4 exome AF: 0.00749 AC: 10476 AN: 1397978 Hom.: 58 Cov.: 29 AF XY: 0.00726 AC XY: 5005 AN XY: 689656

Gnomad4 AFR exome AF: 0.000757

Gnomad4 AMR exome AF: 0.00138

Gnomad4 ASJ exome AF: 0.00605

Gnomad4 EAS exome AF: 0.0000278

Gnomad4 SAS exome AF: 0.000417

Gnomad4 FIN exome AF: 0.00661

Gnomad4 NFE exome AF: 0.00878

Gnomad4 OTH exome AF: 0.00740

GnomAD4 genome AF: 0.00490 AC: 747 AN: 152342 Hom.: 5 Cov.: 33 AF XY: 0.00442 AC XY: 329 AN XY: 74494

Gnomad4 AFR AF: 0.00108

Gnomad4 AMR AF: 0.00150

Gnomad4 ASJ AF: 0.00548

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00660

Gnomad4 NFE AF: 0.00847

Gnomad4 OTH AF: 0.00521

Alfa AF: 0.00726 Hom.: 2

Bravo AF: 0.00421

Asia WGS AF: 0.000578 AC: 2 AN: 3472

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Apr 01, 2023	NBEAL1: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	9.9
DANN	Benign	0.81

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: rs146121994; hg19: chr2-203922075;