14-73279604-C-G

Variant names:

• chr14-73279604-C-G
• rs177380
• NM_001005743.2:c.1097-180G>C

Variant summary

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

The NM_001005743.2(NUMB):​c.1097-180G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.803 in 152,226 control chromosomes in the GnomAD database, including 49,579 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 0.80 (49579 hom., cov: 33)
• Consequence: NUMB NM_001005743.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.249

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.916 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUMB	NM_001005743.2	c.1097-180G>C		intron_variant	Intron 11 of 12	ENST00000555238.6	NP_001005743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUMB	ENST00000555238.6	c.1097-180G>C		intron_variant	Intron 11 of 12	1	NM_001005743.2	ENSP00000451300.1

Frequencies

GnomAD3 genomes AF: 0.802 AC: 122065 AN: 152108 Hom.: 49520 Cov.: 33

Gnomad AFR AF: 0.924

Gnomad AMI AF: 0.666

Gnomad AMR AF: 0.827

Gnomad ASJ AF: 0.737

Gnomad EAS AF: 0.863

Gnomad SAS AF: 0.782

Gnomad FIN AF: 0.809

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.724

Gnomad OTH AF: 0.814

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

GnomAD4 genome AF: 0.803 AC: 122182 AN: 152226 Hom.: 49579 Cov.: 33 AF XY: 0.806 AC XY: 60014 AN XY: 74420

Gnomad4 AFR AF: 0.924

Gnomad4 AMR AF: 0.827

Gnomad4 ASJ AF: 0.737

Gnomad4 EAS AF: 0.864

Gnomad4 SAS AF: 0.783

Gnomad4 FIN AF: 0.809

Gnomad4 NFE AF: 0.724

Gnomad4 OTH AF: 0.809

Alfa AF: 0.758 Hom.: 5143

Bravo AF: 0.812

Asia WGS AF: 0.813 AC: 2827 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.9
DANN	Benign	0.25

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

Other links and lift over

dbSNP: rs177380; hg19: chr14-73746312;