NM_013275.6:c.4932G>A

Variant names:

• chr16-89281610-C-T
• rs72821356
• NM_013275.6:c.4932G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_013275.6(ANKRD11):​c.4932G>A​(p.Gly1644Gly) 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:6
• Conservation: PhyloP100: -0.863
• Publications: 7 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: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, G2P, Illumina, 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 16-89281610-C-T is Benign according to our data. Variant chr16-89281610-C-T is described in ClinVar as Benign. ClinVar VariationId is 380367.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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.

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.4932G>A	p.Gly1644Gly	synonymous	Exon 9 of 13	NP_037407.4
	ANKRD11	NM_001256182.2		c.4932G>A	p.Gly1644Gly	synonymous	Exon 10 of 14	NP_001243111.1
	ANKRD11	NM_001256183.2		c.4932G>A	p.Gly1644Gly	synonymous	Exon 9 of 13	NP_001243112.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD11	ENST00000301030.10	TSL:5 MANE Select	c.4932G>A	p.Gly1644Gly	synonymous	Exon 9 of 13	ENSP00000301030.4
	ANKRD11	ENST00000378330.7	TSL:1	c.4932G>A	p.Gly1644Gly	synonymous	Exon 10 of 14	ENSP00000367581.2
	ANKRD11	ENST00000642600.2		c.4932G>A	p.Gly1644Gly	synonymous	Exon 9 of 13	ENSP00000495226.1

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

GnomAD2 exomes AF: 0.0401 AC: 10063 AN: 250712 AF XY: 0.0393

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 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

African (AFR) AF: 0.00621 AC: 208 AN: 33480

American (AMR) AF: 0.0292 AC: 1305 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0110 AC: 287 AN: 26136

East Asian (EAS) AF: 0.0624 AC: 2478 AN: 39700

South Asian (SAS) AF: 0.0116 AC: 998 AN: 86258

European-Finnish (FIN) AF: 0.122 AC: 6518 AN: 53414

Middle Eastern (MID) AF: 0.00728 AC: 42 AN: 5768

European-Non Finnish (NFE) AF: 0.0393 AC: 43746 AN: 1112012

Other (OTH) AF: 0.0351 AC: 2118 AN: 60396

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

African (AFR) AF: 0.00719 AC: 299 AN: 41562

American (AMR) AF: 0.0245 AC: 375 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00922 AC: 32 AN: 3472

East Asian (EAS) AF: 0.0624 AC: 322 AN: 5164

South Asian (SAS) AF: 0.0159 AC: 77 AN: 4828

European-Finnish (FIN) AF: 0.130 AC: 1374 AN: 10598

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0380 AC: 2586 AN: 67996

Other (OTH) AF: 0.0251 AC: 53 AN: 2114

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

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.46
DANN	Benign	0.20
PhyloP100		-0.86
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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: rs72821356; hg19: chr16-89348018; COSMIC: COSV56357472; COSMIC: COSV56357472;