rs4742741

chr9-98777319-G-A

Variant summary

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

The NM_173551.5(ANKS6):c.1617+86C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.704 in 1,462,558 control chromosomes in the GnomAD database, including 368,083 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.71 (38385 hom., cov: 33)
  • Exomes 𝑓: 0.70 (329698 hom.)
• Consequence: ANKS6 NM_173551.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.457

Genes affected

ANKS6 (HGNC:26724): (ankyrin repeat and sterile alpha motif domain containing 6) This gene encodes a protein containing multiple ankyrin repeats and a SAM domain. It is thought that this protein may localize to the proximal region of the primary cilium, and may play a role in renal and cardiovascular development. Mutations in this gene have been shown to cause a form of nephronophthisis (NPHP16), a chronic tubulo-interstitial nephritis. [provided by RefSeq, Jul 2015]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 9-98777319-G-A is Benign according to our data. Variant chr9-98777319-G-A is described in ClinVar as [Benign]. Clinvar id is 1192473.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.747 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKS6	NM_173551.5	c.1617+86C>T		intron_variant		ENST00000353234.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKS6	ENST00000353234.5	c.1617+86C>T		intron_variant		1	NM_173551.5	P1
ANKS6	ENST00000375019.6	c.714+86C>T		intron_variant		5
ANKS6	ENST00000444472.5	c.22+86C>T		intron_variant		2
ANKS6	ENST00000634393.1	n.717+86C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.705 AC: 107206 AN: 152034 Hom.: 38362 Cov.: 33

Gnomad AFR AF: 0.754

Gnomad AMI AF: 0.771

Gnomad AMR AF: 0.649

Gnomad ASJ AF: 0.753

Gnomad EAS AF: 0.364

Gnomad SAS AF: 0.582

Gnomad FIN AF: 0.646

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.728

Gnomad OTH AF: 0.724

GnomAD4 exome AF: 0.704 AC: 922476 AN: 1310406 Hom.: 329698 AF XY: 0.702 AC XY: 462831 AN XY: 659622

Gnomad4 AFR exome AF: 0.755

Gnomad4 AMR exome AF: 0.558

Gnomad4 ASJ exome AF: 0.765

Gnomad4 EAS exome AF: 0.324

Gnomad4 SAS exome AF: 0.612

Gnomad4 FIN exome AF: 0.657

Gnomad4 NFE exome AF: 0.732

Gnomad4 OTH exome AF: 0.708

GnomAD4 genome AF: 0.705 AC: 107268 AN: 152152 Hom.: 38385 Cov.: 33 AF XY: 0.697 AC XY: 51819 AN XY: 74376

Gnomad4 AFR AF: 0.754

Gnomad4 AMR AF: 0.648

Gnomad4 ASJ AF: 0.753

Gnomad4 EAS AF: 0.364

Gnomad4 SAS AF: 0.583

Gnomad4 FIN AF: 0.646

Gnomad4 NFE AF: 0.728

Gnomad4 OTH AF: 0.720

Alfa AF: 0.719 Hom.: 65494

Bravo AF: 0.705

Asia WGS AF: 0.484 AC: 1686 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Nephronophthisis 16 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
Cadd	Benign	15
Dann	Benign	0.81

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: rs4742741; hg19: chr9-101539601; COSMIC: COSV62048699;