rs2333194

chr14-73300506-G-Achr14-73300506-G-Cchr14-73300506-G-T

Variant summary

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

The NM_001005743.2(NUMB):c.235-3221C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.532 in 151,966 control chromosomes in the GnomAD database, including 22,339 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 0.53 (22339 hom., cov: 31)
• Consequence: NUMB NM_001005743.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.398

Genes affected

NUMB (HGNC:8060): (NUMB endocytic adaptor protein) The protein encoded by this gene plays a role in the determination of cell fates during development. The encoded protein, whose degradation is induced in a proteasome-dependent manner by MDM2, is a membrane-bound protein that has been shown to associate with EPS15, LNX1, and NOTCH1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.707 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NUMB	NM_001005743.2	c.235-3221C>T		intron_variant		ENST00000555238.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUMB	ENST00000555238.6	c.235-3221C>T		intron_variant		1	NM_001005743.2	P4

Frequencies

GnomAD3 genomes AF: 0.532 AC: 80750 AN: 151848 Hom.: 22302 Cov.: 31

Gnomad AFR AF: 0.657

Gnomad AMI AF: 0.423

Gnomad AMR AF: 0.560

Gnomad ASJ AF: 0.491

Gnomad EAS AF: 0.727

Gnomad SAS AF: 0.512

Gnomad FIN AF: 0.562

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.435

Gnomad OTH AF: 0.554

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

GnomAD4 genome AF: 0.532 AC: 80836 AN: 151966 Hom.: 22339 Cov.: 31 AF XY: 0.539 AC XY: 40012 AN XY: 74298

Gnomad4 AFR AF: 0.657

Gnomad4 AMR AF: 0.560

Gnomad4 ASJ AF: 0.491

Gnomad4 EAS AF: 0.727

Gnomad4 SAS AF: 0.513

Gnomad4 FIN AF: 0.562

Gnomad4 NFE AF: 0.435

Gnomad4 OTH AF: 0.548

Alfa AF: 0.444 Hom.: 14519

Bravo AF: 0.539

Asia WGS AF: 0.607 AC: 2109 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.90
Dann	Benign	0.49

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: rs2333194; hg19: chr14-73767214;