rs113358301

Variant names:

• chr18-58044635-C-T
• rs113358301
• NM_001144967.3:c.-26C>T

Your query was ambiguous. Multiple possible variants found:

• chr18-58044635-C-T
• chr18-58044635-C-A
• chr18-58044635-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001144967.3(NEDD4L):​c.-26C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0604 in 1,593,310 control chromosomes in the GnomAD database, including 3,260 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.072 (457 hom., cov: 32)
  • Exomes 𝑓: 0.059 (2803 hom.)
• Consequence: NEDD4L NM_001144967.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.849
• Publications: 5 publications found

Genes affected

NEDD4L (HGNC:7728): (NEDD4 like E3 ubiquitin protein ligase) This gene encodes a member of the Nedd4 family of HECT domain E3 ubiquitin ligases. HECT domain E3 ubiquitin ligases transfer ubiquitin from E2 ubiquitin-conjugating enzymes to protein substrates, thus targeting specific proteins for lysosomal degradation. The encoded protein mediates the ubiquitination of multiple target substrates and plays a critical role in epithelial sodium transport by regulating the cell surface expression of the epithelial sodium channel, ENaC. Single nucleotide polymorphisms in this gene may be associated with essential hypertension. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Mar 2012]

NEDD4L Gene-Disease associations (from GenCC):

• periventricular nodular heterotopia 7

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics
• periventricular nodular heterotopia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 18-58044635-C-T is Benign according to our data. Variant chr18-58044635-C-T is described in ClinVar as Benign. ClinVar VariationId is 1282456.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001144967.3. 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
	NEDD4L	NM_001144967.3	MANE Select	c.-26C>T		5_prime_UTR	Exon 1 of 31	NP_001138439.1	Q96PU5-1
	NEDD4L	NM_015277.6		c.-26C>T		5_prime_UTR	Exon 1 of 30	NP_056092.2
	NEDD4L	NM_001243960.2		c.-26C>T		5_prime_UTR	Exon 1 of 29	NP_001230889.1	Q96PU5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEDD4L	ENST00000400345.8	TSL:1 MANE Select	c.-26C>T		5_prime_UTR	Exon 1 of 31	ENSP00000383199.2	Q96PU5-1
	NEDD4L	ENST00000382850.8	TSL:1	c.-26C>T		5_prime_UTR	Exon 1 of 30	ENSP00000372301.3	Q96PU5-5
	NEDD4L	ENST00000356462.10	TSL:1	c.-26C>T		5_prime_UTR	Exon 1 of 29	ENSP00000348847.5	Q96PU5-2

Frequencies

GnomAD3 genomes AF: 0.0715 AC: 10870 AN: 151958 Hom.: 459 Cov.: 32

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0455

Gnomad ASJ AF: 0.0363

Gnomad EAS AF: 0.00117

Gnomad SAS AF: 0.0375

Gnomad FIN AF: 0.0563

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0612

Gnomad OTH AF: 0.0666

GnomAD2 exomes AF: 0.0508 AC: 11224 AN: 220872 AF XY: 0.0506

Gnomad AFR exome AF: 0.124

Gnomad AMR exome AF: 0.0266

Gnomad ASJ exome AF: 0.0413

Gnomad EAS exome AF: 0.0000641

Gnomad FIN exome AF: 0.0539

Gnomad NFE exome AF: 0.0619

Gnomad OTH exome AF: 0.0549

GnomAD4 exome AF: 0.0593 AC: 85418 AN: 1441240 Hom.: 2803 Cov.: 31 AF XY: 0.0585 AC XY: 41938 AN XY: 716502

African (AFR) AF: 0.125 AC: 3967 AN: 31710

American (AMR) AF: 0.0275 AC: 1181 AN: 42978

Ashkenazi Jewish (ASJ) AF: 0.0410 AC: 1042 AN: 25406

East Asian (EAS) AF: 0.0000794 AC: 3 AN: 37806

South Asian (SAS) AF: 0.0394 AC: 3306 AN: 83892

European-Finnish (FIN) AF: 0.0562 AC: 2906 AN: 51746

Middle Eastern (MID) AF: 0.0530 AC: 300 AN: 5656

European-Non Finnish (NFE) AF: 0.0627 AC: 69104 AN: 1102596

Other (OTH) AF: 0.0607 AC: 3609 AN: 59450

GnomAD4 genome AF: 0.0715 AC: 10875 AN: 152070 Hom.: 457 Cov.: 32 AF XY: 0.0692 AC XY: 5146 AN XY: 74342

African (AFR) AF: 0.119 AC: 4956 AN: 41536

American (AMR) AF: 0.0452 AC: 692 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0363 AC: 126 AN: 3470

East Asian (EAS) AF: 0.00117 AC: 6 AN: 5124

South Asian (SAS) AF: 0.0373 AC: 180 AN: 4826

European-Finnish (FIN) AF: 0.0563 AC: 597 AN: 10602

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0612 AC: 4157 AN: 67898

Other (OTH) AF: 0.0659 AC: 139 AN: 2110

Alfa AF: 0.0351 Hom.: 26

Bravo AF: 0.0737

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.9
DANN	Benign	0.86
PhyloP100		-0.85
PromoterAI		0.0044	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=300/0	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: rs113358301; hg19: chr18-55711867;