rs4742741

Variant names:

• chr9-98777319-G-A
• rs4742741
• NM_173551.5:c.1617+86C>T

Variant summary

Our verdict is Benign. The variant received -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:3
• Conservation: PhyloP100: 0.457
• Publications: 8 publications found

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]

ANKS6 Gene-Disease associations (from GenCC):

• nephronophthisis 16

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)
• nephronophthisis 1

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• nephronophthisis 2

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
ANKS6	NM_173551.5	c.1617+86C>T		intron_variant	Intron 8 of 14	ENST00000353234.5	NP_775822.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKS6	ENST00000353234.5	c.1617+86C>T		intron_variant	Intron 8 of 14	1	NM_173551.5	ENSP00000297837.6
ANKS6	ENST00000375019.6	c.714+86C>T		intron_variant	Intron 7 of 14	5		ENSP00000364159.2
ANKS6	ENST00000444472.5	c.21+86C>T		intron_variant	Intron 1 of 8	2		ENSP00000398648.1
ANKS6	ENST00000634393.1	n.717+86C>T		intron_variant	Intron 6 of 14	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

African (AFR) AF: 0.755 AC: 22794 AN: 30196

American (AMR) AF: 0.558 AC: 24268 AN: 43496

Ashkenazi Jewish (ASJ) AF: 0.765 AC: 18844 AN: 24648

East Asian (EAS) AF: 0.324 AC: 12605 AN: 38924

South Asian (SAS) AF: 0.612 AC: 49955 AN: 81594

European-Finnish (FIN) AF: 0.657 AC: 34776 AN: 52948

Middle Eastern (MID) AF: 0.730 AC: 3972 AN: 5442

European-Non Finnish (NFE) AF: 0.732 AC: 716121 AN: 977898

Other (OTH) AF: 0.708 AC: 39141 AN: 55260

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

African (AFR) AF: 0.754 AC: 31306 AN: 41514

American (AMR) AF: 0.648 AC: 9902 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.753 AC: 2615 AN: 3472

East Asian (EAS) AF: 0.364 AC: 1878 AN: 5162

South Asian (SAS) AF: 0.583 AC: 2813 AN: 4822

European-Finnish (FIN) AF: 0.646 AC: 6833 AN: 10572

Middle Eastern (MID) AF: 0.724 AC: 213 AN: 294

European-Non Finnish (NFE) AF: 0.728 AC: 49483 AN: 68000

Other (OTH) AF: 0.720 AC: 1522 AN: 2114

Alfa AF: 0.719 Hom.: 109746

Bravo AF: 0.705

Asia WGS AF: 0.484 AC: 1686 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nephronophthisis 16 Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	15
DANN	Benign	0.81
PhyloP100		0.46
PromoterAI		0.0068	Neutral
Mutation Taster		=100/0	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: rs4742741; hg19: chr9-101539601; COSMIC: COSV62048699;