dbSNP rs1235547589: ANKRD11:c.*225C>T (chr16-89268253-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_013275.6(ANKRD11):c.*225C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00061 ( 0 hom., cov: 9)

Exomes 𝑓: 0.00098 ( 2 hom. )

Failed GnomAD Quality Control

Consequence

ANKRD11
NM_013275.6 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.821

Variant links:

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 links:

ENSG00000268218 (HGNC:):

ENSG00000268218 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 16-89268253-G-A is Benign according to our data. Variant chr16-89268253-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1189812.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.000981 (215/219238) while in subpopulation MID AF= 0.00459 (4/872). AF 95% confidence interval is 0.00157. There are 2 homozygotes in gnomad4_exome. There are 125 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck.

BS2

High AC in GnomAdExome4 at 215 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ANKRD11	NM_013275.6 link	c.*225C>T	3_prime_UTR_variant	Exon 13 of 13	ENST00000301030.10	NP_037407.4	Q6UB99
ANKRD11	NM_001256182.2 link	c.*225C>T	3_prime_UTR_variant	Exon 14 of 14		NP_001243111.1	Q6UB99
ANKRD11	NM_001256183.2 link	c.*225C>T	3_prime_UTR_variant	Exon 13 of 13		NP_001243112.1	Q6UB99

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKRD11	ENST00000301030 link	c.*225C>T		3_prime_UTR_variant	Exon 13 of 13	5	NM_013275.6	ENSP00000301030.4		Q6UB99

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

76896

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000111

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00531

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000525

Gnomad FIN

AF:

0.000777

Gnomad MID

AF:

0.0116

Gnomad NFE

AF:

0.000662

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000700

AC:

AN:

47132

Hom.:

AF XY:

0.000621

AC XY:

AN XY:

24142

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000126

Gnomad ASJ exome

AF:

0.00633

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000577

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000965

Gnomad OTH exome

AF:

0.00184

GnomAD4 exome

AF:

0.000981

AC:

215

AN:

219238

Hom.:

Cov.:

AF XY:

0.00107

AC XY:

125

AN XY:

116690

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000987

Gnomad4 ASJ exome

AF:

0.00728

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00122

Gnomad4 FIN exome

AF:

0.00105

Gnomad4 NFE exome

AF:

0.000773

Gnomad4 OTH exome

AF:

0.00111

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000611

AC:

AN:

76924

Hom.:

Cov.:

AF XY:

0.000436

AC XY:

AN XY:

32094

show subpopulations

Gnomad4 AFR

AF:

0.000111

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00531

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000527

Gnomad4 FIN

AF:

0.000777

Gnomad4 NFE

AF:

0.000662

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00104

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Aug 31, 2020

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

5.2

DANN

Benign

0.95

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over