rs6855349

Variant names:

• chr4-73091019-G-A
• rs6855349
• NM_032217.5:c.6609C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-73091019-G-A
• chr4-73091019-G-C
• chr4-73091019-G-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_032217.5(ANKRD17):​c.6609C>T​(p.Leu2203Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 1,613,908 control chromosomes in the GnomAD database, including 141,813 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 0.37 (10642 hom., cov: 32)
  • Exomes 𝑓: 0.42 (131171 hom.)
• Consequence: ANKRD17 NM_032217.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.35
• Publications: 20 publications found

Genes affected

ANKRD17 (HGNC:23575): (ankyrin repeat domain 17) The protein encoded by this gene belongs to the family of ankyrin repeat-containing proteins, and contains two distinct arrays of ankyrin repeats in its amino-terminal region, one with 15 ankyrin repeats, and the other with 10 ankyrin repeats. It also contains a nuclear export signal, nuclear localization signal, and a cyclin-binding RXL motif. Localization of this protein to the nucleus has been shown experimentally, and interactions between this protein and cyclin-dependent kinase 2 have been observed. It has been suggested that this protein plays a role in both DNA replication and in both anti-viral and anti-bacterial innate immune pathways. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]

ANKRD17 Gene-Disease associations (from GenCC):

• Chopra-Amiel-Gordon syndrome

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• syndromic intellectual disability

  Inheritance: AD Classification: STRONG Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP7: Synonymous conserved (PhyloP=1.35 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.438 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD17	NM_032217.5	c.6609C>T	p.Leu2203Leu	synonymous_variant	Exon 29 of 34	ENST00000358602.9	NP_115593.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKRD17	ENST00000358602.9	c.6609C>T	p.Leu2203Leu	synonymous_variant	Exon 29 of 34	5	NM_032217.5	ENSP00000351416.4
ANKRD17	ENST00000509867.6	c.6270C>T	p.Leu2090Leu	synonymous_variant	Exon 29 of 34	1		ENSP00000427151.2
ANKRD17	ENST00000558247.5	c.6258C>T	p.Leu2086Leu	synonymous_variant	Exon 29 of 34	1		ENSP00000453434.1
ANKRD17	ENST00000330838.10	c.5856C>T	p.Leu1952Leu	synonymous_variant	Exon 28 of 33	2		ENSP00000332265.6

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55967 AN: 151936 Hom.: 10638 Cov.: 32

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.440

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.373

Gnomad EAS AF: 0.373

Gnomad SAS AF: 0.453

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.430

Gnomad OTH AF: 0.350

GnomAD2 exomes AF: 0.389 AC: 97790 AN: 251388 AF XY: 0.400

Gnomad AFR exome AF: 0.269

Gnomad AMR exome AF: 0.264

Gnomad ASJ exome AF: 0.369

Gnomad EAS exome AF: 0.384

Gnomad FIN exome AF: 0.396

Gnomad NFE exome AF: 0.428

Gnomad OTH exome AF: 0.407

GnomAD4 exome AF: 0.420 AC: 614668 AN: 1461854 Hom.: 131171 Cov.: 70 AF XY: 0.422 AC XY: 307119 AN XY: 727228

African (AFR) AF: 0.267 AC: 8926 AN: 33480

American (AMR) AF: 0.268 AC: 12007 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.375 AC: 9805 AN: 26136

East Asian (EAS) AF: 0.354 AC: 14044 AN: 39700

South Asian (SAS) AF: 0.455 AC: 39225 AN: 86258

European-Finnish (FIN) AF: 0.402 AC: 21466 AN: 53416

Middle Eastern (MID) AF: 0.400 AC: 2307 AN: 5768

European-Non Finnish (NFE) AF: 0.434 AC: 482476 AN: 1111978

Other (OTH) AF: 0.404 AC: 24412 AN: 60396

GnomAD4 genome AF: 0.368 AC: 55997 AN: 152054 Hom.: 10642 Cov.: 32 AF XY: 0.365 AC XY: 27090 AN XY: 74320

African (AFR) AF: 0.271 AC: 11232 AN: 41480

American (AMR) AF: 0.312 AC: 4761 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.373 AC: 1294 AN: 3472

East Asian (EAS) AF: 0.373 AC: 1928 AN: 5172

South Asian (SAS) AF: 0.454 AC: 2184 AN: 4812

European-Finnish (FIN) AF: 0.390 AC: 4110 AN: 10542

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.430 AC: 29239 AN: 67978

Other (OTH) AF: 0.347 AC: 733 AN: 2114

Alfa AF: 0.405 Hom.: 25079

Bravo AF: 0.355

Asia WGS AF: 0.367 AC: 1276 AN: 3478

EpiCase AF: 0.429

EpiControl AF: 0.430

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	4.5
DANN	Benign	0.72
PhyloP100		1.4
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: rs6855349; hg19: chr4-73956736; COSMIC: COSV58216490;