rs9545133

Variant names:

• chr13-79547847-T-C
• rs9545133
• NM_019080.3:c.841-481T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BS1 BS2

The NM_019080.3(NDFIP2):​c.841-481T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0188 in 152,222 control chromosomes in the GnomAD database, including 45 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 0.019 (45 hom., cov: 32)
• Consequence: NDFIP2 NM_019080.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.08
• Publications: 3 publications found

Genes affected

NDFIP2 (HGNC:18537): (Nedd4 family interacting protein 2) Enables WW domain binding activity. Involved in negative regulation of gene expression; negative regulation of transport; and positive regulation of protein ubiquitination. Located in several cellular components, including Golgi apparatus; mitochondrion; and perinuclear region of cytoplasm. [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=-0.25).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0188 (2869/152222) while in subpopulation NFE AF = 0.0294 (1996/67964). AF 95% confidence interval is 0.0283. There are 45 homozygotes in GnomAd4. There are 1375 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 45 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019080.3. 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
	NDFIP2	NM_019080.3	MANE Select	c.841-481T>C		intron	N/A	NP_061953.2
	NDFIP2	NM_001394685.1		c.838-481T>C		intron	N/A	NP_001381614.1
	NDFIP2	NM_001161407.2		c.781-481T>C		intron	N/A	NP_001154879.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDFIP2	ENST00000218652.12	TSL:1 MANE Select	c.841-481T>C		intron	N/A	ENSP00000218652.7
	NDFIP2	ENST00000620924.1	TSL:1	c.559-481T>C		intron	N/A	ENSP00000480881.1
	NDFIP2	ENST00000703122.1		c.559-481T>C		intron	N/A	ENSP00000515183.1

Frequencies

GnomAD3 genomes AF: 0.0189 AC: 2868 AN: 152104 Hom.: 45 Cov.: 32

Gnomad AFR AF: 0.00529

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.0172

Gnomad ASJ AF: 0.0161

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00538

Gnomad FIN AF: 0.0203

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0294

Gnomad OTH AF: 0.0211

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

GnomAD4 genome AF: 0.0188 AC: 2869 AN: 152222 Hom.: 45 Cov.: 32 AF XY: 0.0185 AC XY: 1375 AN XY: 74426

African (AFR) AF: 0.00527 AC: 219 AN: 41556

American (AMR) AF: 0.0171 AC: 262 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0161 AC: 56 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00559 AC: 27 AN: 4830

European-Finnish (FIN) AF: 0.0203 AC: 216 AN: 10616

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0294 AC: 1996 AN: 67964

Other (OTH) AF: 0.0208 AC: 44 AN: 2112

Alfa AF: 0.0232 Hom.: 4

Bravo AF: 0.0177

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	17
DANN	Benign	0.84
PhyloP100		2.1
Mutation Taster		=100/0	polymorphism

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: rs9545133; hg19: chr13-80121982;