chr14-73279604-C-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001005743.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUMB	NM_001005743.2	MANE Select	c.1097-180G>C		intron	N/A	NP_001005743.1	P49757-1
	NUMB	NM_003744.6		c.1064-180G>C		intron	N/A	NP_003735.3
	NUMB	NM_001005744.2		c.1097-2311G>C		intron	N/A	NP_001005744.1	P49757-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUMB	ENST00000555238.6	TSL:1 MANE Select	c.1097-180G>C		intron	N/A	ENSP00000451300.1	P49757-1
	NUMB	ENST00000557597.5	TSL:1	c.1064-180G>C		intron	N/A	ENSP00000451117.1	P49757-3
	NUMB	ENST00000356296.8	TSL:1	c.1097-2311G>C		intron	N/A	ENSP00000348644.4	P49757-2

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

African (AFR) AF: 0.924 AC: 38385 AN: 41556

American (AMR) AF: 0.827 AC: 12650 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.737 AC: 2560 AN: 3472

East Asian (EAS) AF: 0.864 AC: 4473 AN: 5180

South Asian (SAS) AF: 0.783 AC: 3778 AN: 4826

European-Finnish (FIN) AF: 0.809 AC: 8574 AN: 10592

Middle Eastern (MID) AF: 0.694 AC: 204 AN: 294

European-Non Finnish (NFE) AF: 0.724 AC: 49245 AN: 67996

Other (OTH) AF: 0.809 AC: 1706 AN: 2108

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.9
DANN	Benign	0.25
PhyloP100		0.25
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs177380; hg19: chr14-73746312;