19-40681534-A-T

Position:

• chr19-40681534-A-T

Variant summary

Our verdict is Likely benign. Variant got -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

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]

NUMBL (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUMBL	NM_004756.5	c.400-477T>A		intron_variant		ENST00000252891.8	NP_004747.1
NUMBL	NM_001289979.2	c.277-477T>A		intron_variant			NP_001276908.1
NUMBL	NM_001289980.2	c.277-477T>A		intron_variant			NP_001276909.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUMBL	ENST00000252891.8	c.400-477T>A		intron_variant		1	NM_004756.5	ENSP00000252891.3

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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

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: rs2561543; hg19: chr19-41187439;