14-73306901-C-G

Position:

• chr14-73306901-C-G

Variant summary

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

The NM_001005743.2(NUMB):​c.234+9489G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 152,152 control chromosomes in the GnomAD database, including 4,952 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 0.23 (4952 hom., cov: 32)
• Consequence: NUMB NM_001005743.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.94

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]

NUMB (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.657 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUMB	NM_001005743.2	c.234+9489G>C		intron_variant		ENST00000555238.6	NP_001005743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUMB	ENST00000555238.6	c.234+9489G>C		intron_variant		1	NM_001005743.2	ENSP00000451300.1

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34611 AN: 152034 Hom.: 4951 Cov.: 32

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.367

Gnomad ASJ AF: 0.332

Gnomad EAS AF: 0.676

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.254

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.204

Gnomad OTH AF: 0.281

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

GnomAD4 genome AF: 0.228 AC: 34616 AN: 152152 Hom.: 4952 Cov.: 32 AF XY: 0.238 AC XY: 17671 AN XY: 74374

Gnomad4 AFR AF: 0.138

Gnomad4 AMR AF: 0.367

Gnomad4 ASJ AF: 0.332

Gnomad4 EAS AF: 0.676

Gnomad4 SAS AF: 0.246

Gnomad4 FIN AF: 0.254

Gnomad4 NFE AF: 0.204

Gnomad4 OTH AF: 0.277

Alfa AF: 0.215 Hom.: 491

Bravo AF: 0.234

Asia WGS AF: 0.384 AC: 1333 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	18
DANN	Benign	0.54

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: rs10141031; hg19: chr14-73773609;