3-132727492-G-T

Variant names:

• chr3-132727492-G-T
• rs7622700
• ENST00000489343.5:n.697-1G>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 2P and 8B. PVS1_Moderate BA1

The ENST00000489343.5(NPHP3-AS1):​n.697-1G>T variant causes a splice acceptor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 151,578 control chromosomes in the GnomAD database, including 19,533 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.49 (19533 hom., cov: 31)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: NPHP3-AS1 ENST00000489343.5 splice_acceptor, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0830
• Publications: 14 publications found

Genes affected

NPHP3-AS1 (HGNC:24129): (NPHP3 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene. No cryptic splice site detected. Exon removal is inframe change.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.696 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000489343.5. 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
	NPHP3-AS1	NR_002811.2		n.631-1G>T		splice_acceptor intron	N/A
	NPHP3-AS1	NR_152743.1		n.697-1G>T		splice_acceptor intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPHP3-AS1	ENST00000489343.5	TSL:1	n.697-1G>T		splice_acceptor intron	N/A
	NPHP3-AS1	ENST00000504440.1	TSL:1	n.39-1G>T		splice_acceptor intron	N/A

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73450 AN: 151460 Hom.: 19498 Cov.: 31

Gnomad AFR AF: 0.703

Gnomad AMI AF: 0.413

Gnomad AMR AF: 0.389

Gnomad ASJ AF: 0.384

Gnomad EAS AF: 0.679

Gnomad SAS AF: 0.411

Gnomad FIN AF: 0.534

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.364

Gnomad OTH AF: 0.476

GnomAD4 exome AF: 0.250 AC: 1 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.250 AC: 1 AN: 4

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.485 AC: 73535 AN: 151574 Hom.: 19533 Cov.: 31 AF XY: 0.490 AC XY: 36235 AN XY: 74020

African (AFR) AF: 0.703 AC: 29062 AN: 41336

American (AMR) AF: 0.389 AC: 5934 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.384 AC: 1332 AN: 3466

East Asian (EAS) AF: 0.679 AC: 3507 AN: 5168

South Asian (SAS) AF: 0.411 AC: 1975 AN: 4802

European-Finnish (FIN) AF: 0.534 AC: 5556 AN: 10404

Middle Eastern (MID) AF: 0.483 AC: 140 AN: 290

European-Non Finnish (NFE) AF: 0.364 AC: 24661 AN: 67834

Other (OTH) AF: 0.471 AC: 991 AN: 2106

Alfa AF: 0.434 Hom.: 10029

Bravo AF: 0.486

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	14
DANN	Benign	0.88
PhyloP100		-0.083

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7622700; hg19: chr3-132446336;