rs17182398

Positions:

• chr14-73405905-A-C

Variant summary

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

The NM_001005743.2(NUMB):​c.-101+4032T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.039 in 151,198 control chromosomes in the GnomAD database, including 153 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 0.039 (153 hom., cov: 30)
• Consequence: NUMB NM_001005743.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.727

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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUMB	NM_001005743.2	c.-101+4032T>G		intron_variant		ENST00000555238.6	NP_001005743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUMB	ENST00000555238.6	c.-101+4032T>G		intron_variant		1	NM_001005743.2	ENSP00000451300.1

Frequencies

GnomAD3 genomes AF: 0.0390 AC: 5899 AN: 151084 Hom.: 153 Cov.: 30

Gnomad AFR AF: 0.0102

Gnomad AMI AF: 0.0474

Gnomad AMR AF: 0.0413

Gnomad ASJ AF: 0.0954

Gnomad EAS AF: 0.00137

Gnomad SAS AF: 0.0350

Gnomad FIN AF: 0.0373

Gnomad MID AF: 0.0548

Gnomad NFE AF: 0.0562

Gnomad OTH AF: 0.0451

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

GnomAD4 genome AF: 0.0390 AC: 5900 AN: 151198 Hom.: 153 Cov.: 30 AF XY: 0.0384 AC XY: 2836 AN XY: 73866

Gnomad4 AFR AF: 0.0101

Gnomad4 AMR AF: 0.0412

Gnomad4 ASJ AF: 0.0954

Gnomad4 EAS AF: 0.00137

Gnomad4 SAS AF: 0.0356

Gnomad4 FIN AF: 0.0373

Gnomad4 NFE AF: 0.0562

Gnomad4 OTH AF: 0.0451

Alfa AF: 0.0491 Hom.: 104

Bravo AF: 0.0352

Asia WGS AF: 0.0140 AC: 49 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	4.7
DANN	Benign	0.75

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs17182398; hg19: chr14-73872613;