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GeneBe

14-73292839-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_001005743.2(NUMB):c.345T>C(p.Ser115=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00336 in 1,614,244 control chromosomes in the GnomAD database, including 124 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.015 ( 52 hom., cov: 32)
Exomes 𝑓: 0.0021 ( 72 hom. )

Consequence

NUMB
NM_001005743.2 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.629
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 -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.52).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 14-73292839-A-G is Benign according to our data. Variant chr14-73292839-A-G is described in ClinVar as [Benign]. Clinvar id is 768663.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.629 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0513 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NUMBNM_001005743.2 linkuse as main transcriptc.345T>C p.Ser115= synonymous_variant 8/13 ENST00000555238.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NUMBENST00000555238.6 linkuse as main transcriptc.345T>C p.Ser115= synonymous_variant 8/131 NM_001005743.2 P4P49757-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0149
AC:
2276
AN:
152244
Hom.:
51
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0485
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00851
Gnomad ASJ
AF:
0.0219
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000470
Gnomad OTH
AF:
0.0138
GnomAD3 exomes
AF:
0.00458
AC:
1152
AN:
251476
Hom.:
17
AF XY:
0.00367
AC XY:
499
AN XY:
135914
show subpopulations
Gnomad AFR exome
AF:
0.0471
Gnomad AMR exome
AF:
0.00327
Gnomad ASJ exome
AF:
0.0193
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000653
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000536
Gnomad OTH exome
AF:
0.00244
GnomAD4 exome
AF:
0.00215
AC:
3136
AN:
1461882
Hom.:
72
Cov.:
30
AF XY:
0.00192
AC XY:
1398
AN XY:
727242
show subpopulations
Gnomad4 AFR exome
AF:
0.0534
Gnomad4 AMR exome
AF:
0.00380
Gnomad4 ASJ exome
AF:
0.0197
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000266
Gnomad4 OTH exome
AF:
0.00551
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0150
AC:
2281
AN:
152362
Hom.:
52
Cov.:
32
AF XY:
0.0149
AC XY:
1112
AN XY:
74516
show subpopulations
Gnomad4 AFR
AF:
0.0484
Gnomad4 AMR
AF:
0.00850
Gnomad4 ASJ
AF:
0.0219
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000470
Gnomad4 OTH
AF:
0.0137
Alfa
AF:
0.00902
Hom.:
8
Bravo
AF:
0.0171
Asia WGS
AF:
0.00318
AC:
12
AN:
3478
EpiCase
AF:
0.000763
EpiControl
AF:
0.000771

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeMay 30, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.52
Cadd
Benign
11
Dann
Benign
0.69

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

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

Other links and lift over

dbSNP: rs61743309; hg19: chr14-73759547; API