rs2353033

Positions:

• chr16-89319153-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013275.6(ANKRD11):​c.-59-2075G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.514 in 152,150 control chromosomes in the GnomAD database, including 20,631 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 0.51 (20631 hom., cov: 34)
• Consequence: ANKRD11 NM_013275.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.408

Genes affected

LOC128462377 (HGNC:):

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.566 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC128462377	NM_001416403.1	c.10-2078G>A		intron_variant		ENST00000711617.1
ANKRD11	NM_013275.6	c.-59-2075G>A		intron_variant		ENST00000301030.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKRD11	ENST00000301030.10	c.-59-2075G>A		intron_variant		5	NM_013275.6	P1
	ENST00000711617.1	c.10-2078G>A		intron_variant			NM_001416403.1	A2

Frequencies

GnomAD3 genomes AF: 0.515 AC: 78238 AN: 152032 Hom.: 20622 Cov.: 34

Gnomad AFR AF: 0.440

Gnomad AMI AF: 0.625

Gnomad AMR AF: 0.536

Gnomad ASJ AF: 0.683

Gnomad EAS AF: 0.284

Gnomad SAS AF: 0.484

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.571

Gnomad OTH AF: 0.574

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.514 AC: 78268 AN: 152150 Hom.: 20631 Cov.: 34 AF XY: 0.509 AC XY: 37889 AN XY: 74382

Gnomad4 AFR AF: 0.440

Gnomad4 AMR AF: 0.535

Gnomad4 ASJ AF: 0.683

Gnomad4 EAS AF: 0.284

Gnomad4 SAS AF: 0.483

Gnomad4 FIN AF: 0.462

Gnomad4 NFE AF: 0.571

Gnomad4 OTH AF: 0.572

Alfa AF: 0.569 Hom.: 35128

Bravo AF: 0.516

Asia WGS AF: 0.380 AC: 1324 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.5
DANN	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2353033; hg19: chr16-89385561;