rs753852

Positions:

• chr16-89380011-G-A
• chr16-89380011-G-C

Variant summary

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

The NM_013275.6(ANKRD11):​c.-60+38273C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.543 in 151,946 control chromosomes in the GnomAD database, including 22,633 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 0.54 (22633 hom., cov: 32)
• Consequence: ANKRD11 NM_013275.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.668

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.572 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC128462377	NM_001416403.1	c.9+38273C>T		intron_variant		ENST00000711617.1
ANKRD11	NM_013275.6	c.-60+38273C>T		intron_variant		ENST00000301030.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKRD11	ENST00000301030.10	c.-60+38273C>T		intron_variant		5	NM_013275.6	P1
	ENST00000711617.1	c.9+38273C>T		intron_variant			NM_001416403.1	A2

Frequencies

GnomAD3 genomes AF: 0.543 AC: 82403 AN: 151828 Hom.: 22611 Cov.: 32

Gnomad AFR AF: 0.484

Gnomad AMI AF: 0.619

Gnomad AMR AF: 0.565

Gnomad ASJ AF: 0.695

Gnomad EAS AF: 0.590

Gnomad SAS AF: 0.546

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.570

Gnomad OTH AF: 0.622

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

GnomAD4 genome AF: 0.543 AC: 82467 AN: 151946 Hom.: 22633 Cov.: 32 AF XY: 0.540 AC XY: 40070 AN XY: 74250

Gnomad4 AFR AF: 0.484

Gnomad4 AMR AF: 0.565

Gnomad4 ASJ AF: 0.695

Gnomad4 EAS AF: 0.590

Gnomad4 SAS AF: 0.547

Gnomad4 FIN AF: 0.463

Gnomad4 NFE AF: 0.570

Gnomad4 OTH AF: 0.624

Alfa AF: 0.552 Hom.: 3299

Bravo AF: 0.546

Asia WGS AF: 0.592 AC: 2059 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.5
DANN	Benign	0.41

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: rs753852; hg19: chr16-89446419;