5-142108799-G-C

Variant names:

• chr5-142108799-G-C
• rs3761759
• NM_030571.4:c.-176G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030571.4(NDFIP1):​c.-176G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 443,966 control chromosomes in the GnomAD database, including 27,686 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 0.28 (7503 hom., cov: 32)
  • Exomes 𝑓: 0.37 (20183 hom.)
• Consequence: NDFIP1 NM_030571.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.237
• Publications: 8 publications found

Genes affected

NDFIP1 (HGNC:17592): (Nedd4 family interacting protein 1) The protein encoded by this gene belongs to a small group of evolutionarily conserved proteins with three transmembrane domains. It is a potential target for ubiquitination by the Nedd4 family of proteins. This protein is thought to be part of a family of integral Golgi membrane proteins. [provided by RefSeq, Jul 2008]

ENSG00000300089 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030571.4. 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
	NDFIP1	NM_030571.4	MANE Select	c.-176G>C		5_prime_UTR	Exon 1 of 8	NP_085048.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDFIP1	ENST00000253814.6	TSL:1 MANE Select	c.-176G>C		5_prime_UTR	Exon 1 of 8	ENSP00000253814.3
	NDFIP1	ENST00000509436.1	TSL:5	n.12G>C		non_coding_transcript_exon	Exon 1 of 3
	ENSG00000300089	ENST00000768723.1		n.-111C>G		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42443 AN: 151470 Hom.: 7505 Cov.: 32

Gnomad AFR AF: 0.0681

Gnomad AMI AF: 0.494

Gnomad AMR AF: 0.302

Gnomad ASJ AF: 0.390

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.408

Gnomad MID AF: 0.331

Gnomad NFE AF: 0.385

Gnomad OTH AF: 0.307

GnomAD4 exome AF: 0.369 AC: 107848 AN: 292386 Hom.: 20183 Cov.: 5 AF XY: 0.370 AC XY: 55674 AN XY: 150566

African (AFR) AF: 0.0826 AC: 553 AN: 6692

American (AMR) AF: 0.304 AC: 1978 AN: 6510

Ashkenazi Jewish (ASJ) AF: 0.405 AC: 3512 AN: 8676

East Asian (EAS) AF: 0.208 AC: 4267 AN: 20534

South Asian (SAS) AF: 0.276 AC: 3321 AN: 12032

European-Finnish (FIN) AF: 0.412 AC: 8938 AN: 21690

Middle Eastern (MID) AF: 0.337 AC: 422 AN: 1252

European-Non Finnish (NFE) AF: 0.399 AC: 79029 AN: 198242

Other (OTH) AF: 0.348 AC: 5828 AN: 16758

GnomAD4 genome AF: 0.280 AC: 42436 AN: 151580 Hom.: 7503 Cov.: 32 AF XY: 0.279 AC XY: 20692 AN XY: 74072

African (AFR) AF: 0.0679 AC: 2812 AN: 41388

American (AMR) AF: 0.302 AC: 4603 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.390 AC: 1351 AN: 3468

East Asian (EAS) AF: 0.179 AC: 914 AN: 5116

South Asian (SAS) AF: 0.251 AC: 1208 AN: 4806

European-Finnish (FIN) AF: 0.408 AC: 4267 AN: 10448

Middle Eastern (MID) AF: 0.339 AC: 99 AN: 292

European-Non Finnish (NFE) AF: 0.385 AC: 26093 AN: 67808

Other (OTH) AF: 0.305 AC: 643 AN: 2108

Alfa AF: 0.208 Hom.: 530

Bravo AF: 0.263

Asia WGS AF: 0.233 AC: 805 AN: 3442

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	15
DANN	Benign	0.80
PhyloP100		-0.24
PromoterAI		-0.015	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0
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: rs3761759; hg19: chr5-141488364;