rs1019075

Positions:

• chr14-73417339-C-A
• chr14-73417339-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001005743.2(NUMB):​c.-232-7271G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00683 in 151,846 control chromosomes in the GnomAD database, including 5 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 0.0068 (5 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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00683 (1037/151846) while in subpopulation SAS AF= 0.0297 (143/4816). AF 95% confidence interval is 0.0257. There are 5 homozygotes in gnomad4. There are 565 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1037 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUMB	NM_001005743.2	c.-232-7271G>T		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>T		intron_variant		1	NM_001005743.2	ENSP00000451300	P4

Frequencies

GnomAD3 genomes AF: 0.00681 AC: 1034 AN: 151726 Hom.: 5 Cov.: 30

Gnomad AFR AF: 0.00805

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00479

Gnomad ASJ AF: 0.0231

Gnomad EAS AF: 0.0175

Gnomad SAS AF: 0.0295

Gnomad FIN AF: 0.00370

Gnomad MID AF: 0.00962

Gnomad NFE AF: 0.00375

Gnomad OTH AF: 0.00958

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

GnomAD4 genome AF: 0.00683 AC: 1037 AN: 151846 Hom.: 5 Cov.: 30 AF XY: 0.00762 AC XY: 565 AN XY: 74174

Gnomad4 AFR AF: 0.00805

Gnomad4 AMR AF: 0.00478

Gnomad4 ASJ AF: 0.0231

Gnomad4 EAS AF: 0.0176

Gnomad4 SAS AF: 0.0297

Gnomad4 FIN AF: 0.00370

Gnomad4 NFE AF: 0.00375

Gnomad4 OTH AF: 0.00995

Alfa AF: 0.00129 Hom.: 699

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.0
DANN	Benign	0.68

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;