14-73417339-C-T

Position:

• chr14-73417339-C-T

Variant summary

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

The NM_001005743.2(NUMB):​c.-232-7271G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.473 in 151,750 control chromosomes in the GnomAD database, including 17,585 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 0.47 (17585 hom., cov: 30)
• Consequence: NUMB NM_001005743.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305

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]

ENSG00000285006 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.794 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUMB	NM_001005743.2	c.-232-7271G>A		intron_variant		ENST00000555238.6	NP_001005743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUMB	ENST00000555238.6	c.-232-7271G>A		intron_variant		1	NM_001005743.2	ENSP00000451300.1

Frequencies

GnomAD3 genomes AF: 0.473 AC: 71673 AN: 151630 Hom.: 17574 Cov.: 30

Gnomad AFR AF: 0.398

Gnomad AMI AF: 0.427

Gnomad AMR AF: 0.610

Gnomad ASJ AF: 0.527

Gnomad EAS AF: 0.815

Gnomad SAS AF: 0.483

Gnomad FIN AF: 0.470

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.457

Gnomad OTH AF: 0.515

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

GnomAD4 genome AF: 0.473 AC: 71705 AN: 151750 Hom.: 17585 Cov.: 30 AF XY: 0.480 AC XY: 35569 AN XY: 74126

Gnomad4 AFR AF: 0.398

Gnomad4 AMR AF: 0.610

Gnomad4 ASJ AF: 0.527

Gnomad4 EAS AF: 0.815

Gnomad4 SAS AF: 0.483

Gnomad4 FIN AF: 0.470

Gnomad4 NFE AF: 0.457

Gnomad4 OTH AF: 0.513

Alfa AF: 0.304 Hom.: 699

Bravo AF: 0.487

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.7
DANN	Benign	0.63

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1019075; hg19: chr14-73884047;