15-55832937-C-G

Variant names:

• chr15-55832937-C-G
• rs8024944
• NM_006154.4:c.2527+71G>C

Variant summary

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

The NM_006154.4(NEDD4):​c.2527+71G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000697 in 861,422 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000070 (0 hom.)
• Consequence: NEDD4 NM_006154.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.738
• Publications: 0 publications found

Genes affected

NEDD4 (HGNC:7727): (NEDD4 E3 ubiquitin protein ligase) This gene is the founding member of the NEDD4 family of HECT ubiquitin ligases that function in the ubiquitin proteasome system of protein degradation. The encoded protein contains an N-terminal calcium and phospholipid binding C2 domain followed by multiple tryptophan-rich WW domains and, a C-terminal HECT ubiquitin ligase catalytic domain. It plays critical role in the regulation of a number of membrane receptors, endocytic machinery components and the tumor suppressor PTEN. [provided by RefSeq, Jul 2016]

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_006154.4. 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
	NEDD4	NM_006154.4	MANE Select	c.2527+71G>C		intron	N/A	NP_006145.2	P46934-4
	NEDD4	NM_001284338.2		c.3784+71G>C		intron	N/A	NP_001271267.1	P46934-1
	NEDD4	NM_001284339.1		c.3736+71G>C		intron	N/A	NP_001271268.1	P46934-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEDD4	ENST00000435532.8	TSL:1 MANE Select	c.2527+71G>C		intron	N/A	ENSP00000410613.3	P46934-4
	NEDD4	ENST00000508342.5	TSL:1	c.3784+71G>C		intron	N/A	ENSP00000424827.1	P46934-1
	NEDD4	ENST00000506154.1	TSL:1	c.3736+71G>C		intron	N/A	ENSP00000422705.1	P46934-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000697 AC: 6 AN: 861422 Hom.: 0 AF XY: 0.0000112 AC XY: 5 AN XY: 444864

African (AFR) AF: 0.00 AC: 0 AN: 20738

American (AMR) AF: 0.00 AC: 0 AN: 32296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19174

East Asian (EAS) AF: 0.00 AC: 0 AN: 36430

South Asian (SAS) AF: 0.0000970 AC: 6 AN: 61850

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48080

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4418

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 598888

Other (OTH) AF: 0.00 AC: 0 AN: 39548

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.5
DANN	Benign	0.075
PhyloP100		0.74

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: rs8024944; hg19: chr15-56125135;