chr1-179552797-G-T

Position:

• chr1-179552797-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_144696.6(AXDND1):​c.3032-1715G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 785,896 control chromosomes in the GnomAD database, including 58,824 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.42 (13881 hom., cov: 33)
  • Exomes 𝑓: 0.37 (44943 hom.)
• Consequence: AXDND1 NM_144696.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.331

Genes affected

NPHS2 (HGNC:13394): (NPHS2 stomatin family member, podocin) This gene encodes a protein that plays a role in the regulation of glomerular permeability. Mutations in this gene cause steroid-resistant nephrotic syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

AXDND1 (HGNC:26564): (axonemal dynein light chain domain containing 1)

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 1-179552797-G-T is Benign according to our data. Variant chr1-179552797-G-T is described in ClinVar as [Benign]. Clinvar id is 1289362.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPHS2	NM_014625.4	c.795-116C>A		intron_variant		ENST00000367615.9
AXDND1	NM_144696.6	c.3032-1715G>T		intron_variant		ENST00000367618.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPHS2	ENST00000367615.9	c.795-116C>A		intron_variant		1	NM_014625.4	P1
AXDND1	ENST00000367618.8	c.3032-1715G>T		intron_variant		1	NM_144696.6	P2

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63300 AN: 151974 Hom.: 13856 Cov.: 33

Gnomad AFR AF: 0.553

Gnomad AMI AF: 0.438

Gnomad AMR AF: 0.437

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.432

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.352

Gnomad OTH AF: 0.405

GnomAD4 exome AF: 0.373 AC: 236209 AN: 633804 Hom.: 44943 AF XY: 0.372 AC XY: 125923 AN XY: 338374

Gnomad4 AFR exome AF: 0.556

Gnomad4 AMR exome AF: 0.428

Gnomad4 ASJ exome AF: 0.311

Gnomad4 EAS exome AF: 0.446

Gnomad4 SAS exome AF: 0.395

Gnomad4 FIN exome AF: 0.313

Gnomad4 NFE exome AF: 0.357

Gnomad4 OTH exome AF: 0.385

GnomAD4 genome AF: 0.417 AC: 63373 AN: 152092 Hom.: 13881 Cov.: 33 AF XY: 0.414 AC XY: 30794 AN XY: 74364

Gnomad4 AFR AF: 0.553

Gnomad4 AMR AF: 0.436

Gnomad4 ASJ AF: 0.297

Gnomad4 EAS AF: 0.432

Gnomad4 SAS AF: 0.397

Gnomad4 FIN AF: 0.311

Gnomad4 NFE AF: 0.352

Gnomad4 OTH AF: 0.408

Alfa AF: 0.359 Hom.: 13196

Bravo AF: 0.434

Asia WGS AF: 0.459 AC: 1598 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.91
DANN	Benign	0.50

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

Publications

LitVar

Other links and lift over

dbSNP: rs2274626; hg19: chr1-179521932;