rs7202

Variant names:

• chr14-73275573-G-A
• rs7202
• NM_001005743.2:c.*1005C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001005743.2(NUMB):​c.*1005C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 151,892 control chromosomes in the GnomAD database, including 4,911 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 0.25 (4911 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NUMB NM_001005743.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.949
• Publications: 11 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.24).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUMB	NM_001005743.2	c.*1005C>T		3_prime_UTR_variant	Exon 13 of 13	ENST00000555238.6	NP_001005743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUMB	ENST00000555238.6	c.*1005C>T		3_prime_UTR_variant	Exon 13 of 13	1	NM_001005743.2	ENSP00000451300.1

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38284 AN: 151774 Hom.: 4912 Cov.: 32

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.245

Gnomad AMR AF: 0.259

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.128

Gnomad SAS AF: 0.267

Gnomad FIN AF: 0.247

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.249

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.252 AC: 38305 AN: 151892 Hom.: 4911 Cov.: 32 AF XY: 0.250 AC XY: 18572 AN XY: 74224

African (AFR) AF: 0.216 AC: 8958 AN: 41394

American (AMR) AF: 0.259 AC: 3958 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.225 AC: 781 AN: 3464

East Asian (EAS) AF: 0.129 AC: 665 AN: 5166

South Asian (SAS) AF: 0.266 AC: 1278 AN: 4804

European-Finnish (FIN) AF: 0.247 AC: 2607 AN: 10538

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.283 AC: 19245 AN: 67958

Other (OTH) AF: 0.251 AC: 528 AN: 2104

Alfa AF: 0.279 Hom.: 3442

Bravo AF: 0.251

Asia WGS AF: 0.190 AC: 663 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.24
CADD	Benign	11
DANN	Benign	0.87
PhyloP100		0.95
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: rs7202; hg19: chr14-73742281;