NM_004756.5:c.400-477T>A

Variant names:

• chr19-40681534-A-T
• rs2561543
• NM_004756.5:c.400-477T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004756.5(NUMBL):​c.400-477T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: NUMBL NM_004756.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.286
• Publications: 11 publications found

Genes affected

NUMBL (HGNC:8061): (NUMB like endocytic adaptor protein) Involved in cytokine-mediated signaling pathway and protein metabolic process. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004756.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUMBL	NM_004756.5	MANE Select	c.400-477T>A		intron	N/A	NP_004747.1
	NUMBL	NM_001289979.2		c.277-477T>A		intron	N/A	NP_001276908.1
	NUMBL	NM_001289980.2		c.277-477T>A		intron	N/A	NP_001276909.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUMBL	ENST00000252891.8	TSL:1 MANE Select	c.400-477T>A		intron	N/A	ENSP00000252891.3
	NUMBL	ENST00000598779.5	TSL:1	c.277-477T>A		intron	N/A	ENSP00000472400.1
	NUMBL	ENST00000540131.5	TSL:2	c.277-477T>A		intron	N/A	ENSP00000442759.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 17737

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.9
DANN	Benign	0.78
PhyloP100		0.29

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: rs2561543; hg19: chr19-41187439;