rs72821356

chr16-89281610-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_013275.6(ANKRD11):c.4932G>A(p.Gly1644=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0389 in 1,614,124 control chromosomes in the GnomAD database, including 1,585 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.034 (153 hom., cov: 32)
  • Exomes 𝑓: 0.039 (1432 hom.)
• Consequence: ANKRD11 NM_013275.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.863

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 16-89281610-C-T is Benign according to our data. Variant chr16-89281610-C-T is described in ClinVar as [Benign]. Clinvar id is 380367.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-89281610-C-T is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.863 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKRD11	NM_013275.6	c.4932G>A	p.Gly1644=	synonymous_variant	9/13	ENST00000301030.10
ANKRD11	NM_001256182.2	c.4932G>A	p.Gly1644=	synonymous_variant	10/14
ANKRD11	NM_001256183.2	c.4932G>A	p.Gly1644=	synonymous_variant	9/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKRD11	ENST00000301030.10	c.4932G>A	p.Gly1644=	synonymous_variant	9/13	5	NM_013275.6	P1

Frequencies

GnomAD3 genomes AF: 0.0337 AC: 5119 AN: 152118 Hom.: 153 Cov.: 32

Gnomad AFR AF: 0.00722

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0246

Gnomad ASJ AF: 0.00922

Gnomad EAS AF: 0.0620

Gnomad SAS AF: 0.0157

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0380

Gnomad OTH AF: 0.0253

GnomAD3 exomes AF: 0.0401 AC: 10063 AN: 250712 Hom.: 371 AF XY: 0.0393 AC XY: 5339 AN XY: 135760

Gnomad AFR exome AF: 0.00750

Gnomad AMR exome AF: 0.0284

Gnomad ASJ exome AF: 0.0102

Gnomad EAS exome AF: 0.0665

Gnomad SAS exome AF: 0.00960

Gnomad FIN exome AF: 0.127

Gnomad NFE exome AF: 0.0382

Gnomad OTH exome AF: 0.0426

GnomAD4 exome AF: 0.0395 AC: 57700 AN: 1461888 Hom.: 1432 Cov.: 35 AF XY: 0.0385 AC XY: 27975 AN XY: 727248

Gnomad4 AFR exome AF: 0.00621

Gnomad4 AMR exome AF: 0.0292

Gnomad4 ASJ exome AF: 0.0110

Gnomad4 EAS exome AF: 0.0624

Gnomad4 SAS exome AF: 0.0116

Gnomad4 FIN exome AF: 0.122

Gnomad4 NFE exome AF: 0.0393

Gnomad4 OTH exome AF: 0.0351

GnomAD4 genome AF: 0.0336 AC: 5120 AN: 152236 Hom.: 153 Cov.: 32 AF XY: 0.0375 AC XY: 2788 AN XY: 74422

Gnomad4 AFR AF: 0.00719

Gnomad4 AMR AF: 0.0245

Gnomad4 ASJ AF: 0.00922

Gnomad4 EAS AF: 0.0624

Gnomad4 SAS AF: 0.0159

Gnomad4 FIN AF: 0.130

Gnomad4 NFE AF: 0.0380

Gnomad4 OTH AF: 0.0251

Alfa AF: 0.0325 Hom.: 46

Bravo AF: 0.0251

Asia WGS AF: 0.0410 AC: 143 AN: 3478

EpiCase AF: 0.0306

EpiControl AF: 0.0293

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 22, 2015	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. -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jun 28, 2017	- -

KBG syndrome Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 30, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Dec 05, 2021	- -

Inborn genetic diseases Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 19, 2016

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.46
Dann	Benign	0.20
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs72821356; hg19: chr16-89348018; COSMIC: COSV56357472; COSMIC: COSV56357472;