chr2-203077786-T-C

Variant names:

• chr2-203077786-T-C
• rs902384156
• NM_001378026.1:c.633T>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001378026.1(NBEAL1):​c.633T>C​(p.Ser211Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NBEAL1 NM_001378026.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.434
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP7: Synonymous conserved (PhyloP=0.434 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NBEAL1	NM_001378026.1	c.633T>C	p.Ser211Ser	synonymous_variant	Exon 8 of 56	ENST00000683969.1	NP_001364955.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NBEAL1	ENST00000683969.1	c.633T>C	p.Ser211Ser	synonymous_variant	Exon 8 of 56		NM_001378026.1	ENSP00000508055.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1318992 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 647102

African (AFR) AF: 0.00 AC: 0 AN: 29288

American (AMR) AF: 0.00 AC: 0 AN: 29918

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23488

East Asian (EAS) AF: 0.00 AC: 0 AN: 33072

South Asian (SAS) AF: 0.00 AC: 0 AN: 60470

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45974

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4370

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1038268

Other (OTH) AF: 0.00 AC: 0 AN: 54144

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	9.7
DANN	Benign	0.77
PhyloP100		0.43
Mutation Taster		=100/0	polymorphism

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: rs902384156; hg19: chr2-203942509;