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]

PAPLN (HGNC:19262): (papilin, proteoglycan like sulfated glycoprotein) Predicted to enable metalloendopeptidase activity. Predicted to be involved in extracellular matrix organization. Predicted to be located in basement membrane. Predicted to be active in extracellular matrix. [provided by Alliance of Genome Resources, Apr 2022]

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.

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.*1005C>T		3_prime_UTR	Exon 13 of 13	NP_001005743.1
	NUMB	NM_003744.6		c.*1005C>T		3_prime_UTR	Exon 12 of 12	NP_003735.3
	NUMB	NM_001005744.2		c.*1005C>T		3_prime_UTR	Exon 12 of 12	NP_001005744.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUMB	ENST00000555238.6	TSL:1 MANE Select	c.*1005C>T		3_prime_UTR	Exon 13 of 13	ENSP00000451300.1
	NUMB	ENST00000557597.5	TSL:1	c.*1005C>T		3_prime_UTR	Exon 12 of 12	ENSP00000451117.1
	NUMB	ENST00000356296.8	TSL:1	c.*1005C>T		3_prime_UTR	Exon 12 of 12	ENSP00000348644.4

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 v4.9

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;