rs753852

Variant names:

• chr16-89380011-G-A
• rs753852
• NM_013275.6:c.-60+38273C>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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

ENSG00000288715 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ANKRD11	NM_013275.6	c.-60+38273C>T		intron_variant	Intron 2 of 12	ENST00000301030.10	NP_037407.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKRD11	ENST00000301030.10	c.-60+38273C>T		intron_variant	Intron 2 of 12	5	NM_013275.6	ENSP00000301030.4
ENSG00000288715	ENST00000711617.1	c.9+38273C>T		intron_variant	Intron 1 of 1			ENSP00000518812.1

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

African (AFR) AF: 0.484 AC: 20075 AN: 41454

American (AMR) AF: 0.565 AC: 8627 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.695 AC: 2413 AN: 3470

East Asian (EAS) AF: 0.590 AC: 3042 AN: 5160

South Asian (SAS) AF: 0.547 AC: 2630 AN: 4804

European-Finnish (FIN) AF: 0.463 AC: 4872 AN: 10522

Middle Eastern (MID) AF: 0.741 AC: 218 AN: 294

European-Non Finnish (NFE) AF: 0.570 AC: 38712 AN: 67950

Other (OTH) AF: 0.624 AC: 1317 AN: 2110

Alfa AF: 0.550 Hom.: 3402

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
PhyloP100		0.67
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: rs753852; hg19: chr16-89446419;