14-73417339-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.305
Variant links:
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]

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ACMG classification

Classification made for transcript

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
NUMBNM_001005743.2 linkuse as main transcriptc.-232-7271G>A intron_variant ENST00000555238.6 NP_001005743.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NUMBENST00000555238.6 linkuse as main transcriptc.-232-7271G>A intron_variant 1 NM_001005743.2 ENSP00000451300 P4P49757-1

Frequencies

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1019075; hg19: chr14-73884047; API