rs2086824

Positions:

• chr16-89404838-A-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_013275.6(ANKRD11):​c.-60+13446T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 152,184 control chromosomes in the GnomAD database, including 10,831 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 0.33 (10831 hom., cov: 32)
• Consequence: ANKRD11 NM_013275.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.132

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.477 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC128462377	NM_001416403.1	c.9+13446T>G		intron_variant		ENST00000711617.1
ANKRD11	NM_013275.6	c.-60+13446T>G		intron_variant		ENST00000301030.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKRD11	ENST00000301030.10	c.-60+13446T>G		intron_variant		5	NM_013275.6	P1
	ENST00000711617.1	c.9+13446T>G		intron_variant			NM_001416403.1	A2

Frequencies

GnomAD3 genomes AF: 0.333 AC: 50568 AN: 152066 Hom.: 10833 Cov.: 32

Gnomad AFR AF: 0.0937

Gnomad AMI AF: 0.535

Gnomad AMR AF: 0.353

Gnomad ASJ AF: 0.579

Gnomad EAS AF: 0.0467

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.352

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.481

Gnomad OTH AF: 0.436

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

GnomAD4 genome AF: 0.332 AC: 50549 AN: 152184 Hom.: 10831 Cov.: 32 AF XY: 0.322 AC XY: 23976 AN XY: 74398

Gnomad4 AFR AF: 0.0935

Gnomad4 AMR AF: 0.352

Gnomad4 ASJ AF: 0.579

Gnomad4 EAS AF: 0.0466

Gnomad4 SAS AF: 0.216

Gnomad4 FIN AF: 0.352

Gnomad4 NFE AF: 0.481

Gnomad4 OTH AF: 0.430

Alfa AF: 0.461 Hom.: 18128

Bravo AF: 0.325

Asia WGS AF: 0.127 AC: 442 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	15
DANN	Benign	0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.29		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.29		Position offset: 0

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2086824; hg19: chr16-89471246;