16-89281670-C-T

Variant names:

• chr16-89281670-C-T
• rs143426579
• NM_013275.6:c.4872G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_013275.6(ANKRD11):​c.4872G>A​(p.Ala1624Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00685 in 1,614,162 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. A1624A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0042 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0071 (46 hom.)
• Consequence: ANKRD11 NM_013275.6 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -2.11
• Publications: 3 publications found

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]

ANKRD11 Gene-Disease associations (from GenCC):

• KBG syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, G2P, Illumina, Labcorp Genetics (formerly Invitae), Orphanet, ClinGen
• congenital heart defects, multiple types

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 16-89281670-C-T is Benign according to our data. Variant chr16-89281670-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 446826.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.11 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00423 (645/152306) while in subpopulation NFE AF = 0.00723 (492/68026). AF 95% confidence interval is 0.0067. There are 0 homozygotes in GnomAd4. There are 296 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 645 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013275.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD11	NM_013275.6	MANE Select	c.4872G>A	p.Ala1624Ala	synonymous	Exon 9 of 13	NP_037407.4
	ANKRD11	NM_001256182.2		c.4872G>A	p.Ala1624Ala	synonymous	Exon 10 of 14	NP_001243111.1	Q6UB99
	ANKRD11	NM_001256183.2		c.4872G>A	p.Ala1624Ala	synonymous	Exon 9 of 13	NP_001243112.1	Q6UB99

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD11	ENST00000301030.10	TSL:5 MANE Select	c.4872G>A	p.Ala1624Ala	synonymous	Exon 9 of 13	ENSP00000301030.4	Q6UB99
	ANKRD11	ENST00000378330.7	TSL:1	c.4872G>A	p.Ala1624Ala	synonymous	Exon 10 of 14	ENSP00000367581.2	Q6UB99
	ANKRD11	ENST00000642600.2		c.4872G>A	p.Ala1624Ala	synonymous	Exon 9 of 13	ENSP00000495226.1	Q6UB99

Frequencies

GnomAD3 genomes AF: 0.00424 AC: 646 AN: 152188 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00268

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00455

Gnomad FIN AF: 0.00122

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00723

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00457 AC: 1148 AN: 251206 AF XY: 0.00465

Gnomad AFR exome AF: 0.00130

Gnomad AMR exome AF: 0.00156

Gnomad ASJ exome AF: 0.00705

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000740

Gnomad NFE exome AF: 0.00717

Gnomad OTH exome AF: 0.00555

GnomAD4 exome AF: 0.00713 AC: 10420 AN: 1461856 Hom.: 46 Cov.: 35 AF XY: 0.00689 AC XY: 5008 AN XY: 727230

African (AFR) AF: 0.000807 AC: 27 AN: 33478

American (AMR) AF: 0.00183 AC: 82 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00601 AC: 157 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00434 AC: 374 AN: 86258

European-Finnish (FIN) AF: 0.000899 AC: 48 AN: 53402

Middle Eastern (MID) AF: 0.00589 AC: 34 AN: 5768

European-Non Finnish (NFE) AF: 0.00828 AC: 9209 AN: 1111998

Other (OTH) AF: 0.00810 AC: 489 AN: 60392

GnomAD4 genome AF: 0.00423 AC: 645 AN: 152306 Hom.: 0 Cov.: 32 AF XY: 0.00398 AC XY: 296 AN XY: 74464

African (AFR) AF: 0.00144 AC: 60 AN: 41568

American (AMR) AF: 0.00268 AC: 41 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00288 AC: 10 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00435 AC: 21 AN: 4830

European-Finnish (FIN) AF: 0.00122 AC: 13 AN: 10618

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00723 AC: 492 AN: 68026

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.00443 Hom.: 0

Bravo AF: 0.00436

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.00769

EpiControl AF: 0.00729

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	2	KBG syndrome (2)
-	-	2	not specified (2)
-	-	1	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.76
DANN	Benign	0.45
PhyloP100		-2.1
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.1
Mutation Taster		=99/1	polymorphism

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: rs143426579; hg19: chr16-89348078; COSMIC: COSV56374246; COSMIC: COSV56374246;