rs147328392

chr16-89288510-G-Cchr16-89288510-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_013275.6(ANKRD11):c.744+18C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00646 in 1,614,056 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0042 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0067 (47 hom.)
• Consequence: ANKRD11 NM_013275.6 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.513

Genes affected

ANKRD11 (HGNC:21316): (ankyrin repeat domain containing 11) This locus encodes an ankryin repeat domain-containing protein. The encoded protein inhibits ligand-dependent activation of transcription. Mutations in this gene have been associated with KBG syndrome, which is characterized by macrodontia, distinctive craniofacial features, short stature, skeletal anomalies, global developmental delay, seizures and intellectual disability. Alternatively spliced transcript variants have been described. Related pseudogenes exist on chromosomes 2 and X. [provided by RefSeq, Jan 2012]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0046622455).
• BP6: Variant 16-89288510-G-C is Benign according to our data. Variant chr16-89288510-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 445449.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-89288510-G-C is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00421 (641/152332) while in subpopulation NFE AF= 0.00703 (478/68032). AF 95% confidence interval is 0.00651. There are 1 homozygotes in gnomad4. There are 288 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 641 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKRD11	NM_013275.6	c.744+18C>G		intron_variant		ENST00000301030.10
ANKRD11	NM_001256182.2	c.744+18C>G		intron_variant
ANKRD11	NM_001256183.2	c.744+18C>G		intron_variant
ANKRD11	NR_045839.2	n.1575+18C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKRD11	ENST00000301030.10	c.744+18C>G		intron_variant		5	NM_013275.6	P1

Frequencies

GnomAD3 genomes AF: 0.00421 AC: 641 AN: 152214 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00109

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00262

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00640

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00703

Gnomad OTH AF: 0.00334

GnomAD3 exomes AF: 0.00393 AC: 986 AN: 250912 Hom.: 4 AF XY: 0.00377 AC XY: 512 AN XY: 135736

Gnomad AFR exome AF: 0.000863

Gnomad AMR exome AF: 0.00217

Gnomad ASJ exome AF: 0.00219

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000294

Gnomad FIN exome AF: 0.00718

Gnomad NFE exome AF: 0.00598

Gnomad OTH exome AF: 0.00539

GnomAD4 exome AF: 0.00670 AC: 9787 AN: 1461724 Hom.: 47 Cov.: 31 AF XY: 0.00652 AC XY: 4741 AN XY: 727166

Gnomad4 AFR exome AF: 0.000806

Gnomad4 AMR exome AF: 0.00212

Gnomad4 ASJ exome AF: 0.00191

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000267

Gnomad4 FIN exome AF: 0.00660

Gnomad4 NFE exome AF: 0.00800

Gnomad4 OTH exome AF: 0.00568

GnomAD4 genome AF: 0.00421 AC: 641 AN: 152332 Hom.: 1 Cov.: 33 AF XY: 0.00387 AC XY: 288 AN XY: 74494

Gnomad4 AFR AF: 0.00108

Gnomad4 AMR AF: 0.00261

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00640

Gnomad4 NFE AF: 0.00703

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00513 Hom.: 0

Bravo AF: 0.00373

TwinsUK AF: 0.00728 AC: 27

ALSPAC AF: 0.00649 AC: 25

ESP6500AA AF: 0.00114 AC: 5

ESP6500EA AF: 0.00721 AC: 62

ExAC AF: 0.00385 AC: 468

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

KBG syndrome Benign:3

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Dec 05, 2021	- -
Likely benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	May 16, 2022	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Apr 01, 2024	ANKRD11: BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Sep 27, 2017	- -

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 02, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	8.2
Dann	Benign	0.31
FATHMM_MKL	Benign	0.031	N
MetaRNN	Benign	0.0047	T;T;T;T
MutationTaster	Benign	1.0	N;N
GERP RS		-1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs147328392; hg19: chr16-89354918;