rs147328392

Variant names:

• chr16-89288510-G-C
• rs147328392
• NM_013275.6:c.744+18C>G

Your query was ambiguous. Multiple possible variants found:

• chr16-89288510-G-C
• chr16-89288510-G-A
• chr16-89288510-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_013275.6(ANKRD11):​c.744+18C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00646 in 1,614,056 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0042 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0067 (47 hom.)
• Consequence: ANKRD11 NM_013275.6 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.513
• Publications: 0 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: Ambry Genetics, G2P, Illumina, Labcorp Genetics (formerly Invitae), Orphanet, ClinGen
• congenital heart defects, multiple types

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0046622455).
• BP6: Variant 16-89288510-G-C is Benign according to our data. Variant chr16-89288510-G-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 445449.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00421 (641/152332) while in subpopulation NFE AF = 0.00703 (478/68032). AF 95% confidence interval is 0.00651. There are 1 homozygotes in GnomAd4. There are 288 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 641 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013275.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD11	NM_013275.6	MANE Select	c.744+18C>G		intron	N/A	NP_037407.4
	ANKRD11	NM_001256182.2		c.744+18C>G		intron	N/A	NP_001243111.1	Q6UB99
	ANKRD11	NM_001256183.2		c.744+18C>G		intron	N/A	NP_001243112.1	Q6UB99

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD11	ENST00000301030.10	TSL:5 MANE Select	c.744+18C>G		intron	N/A	ENSP00000301030.4	Q6UB99
	ANKRD11	ENST00000378330.7	TSL:1	c.744+18C>G		intron	N/A	ENSP00000367581.2	Q6UB99
	ANKRD11	ENST00000642333.1		c.762C>G	p.Phe254Leu	missense	Exon 8 of 8	ENSP00000496651.1	A0A2R8YE03

Frequencies

GnomAD3 genomes AF: 0.00421 AC: 641 AN: 152214 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00109

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00262

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00640

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00703

Gnomad OTH AF: 0.00334

GnomAD2 exomes AF: 0.00393 AC: 986 AN: 250912 AF XY: 0.00377

Gnomad AFR exome AF: 0.000863

Gnomad AMR exome AF: 0.00217

Gnomad ASJ exome AF: 0.00219

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00718

Gnomad NFE exome AF: 0.00598

Gnomad OTH exome AF: 0.00539

GnomAD4 exome AF: 0.00670 AC: 9787 AN: 1461724 Hom.: 47 Cov.: 31 AF XY: 0.00652 AC XY: 4741 AN XY: 727166

African (AFR) AF: 0.000806 AC: 27 AN: 33480

American (AMR) AF: 0.00212 AC: 95 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00191 AC: 50 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000267 AC: 23 AN: 86250

European-Finnish (FIN) AF: 0.00660 AC: 352 AN: 53310

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.00800 AC: 8896 AN: 1111984

Other (OTH) AF: 0.00568 AC: 343 AN: 60390

GnomAD4 genome AF: 0.00421 AC: 641 AN: 152332 Hom.: 1 Cov.: 33 AF XY: 0.00387 AC XY: 288 AN XY: 74494

African (AFR) AF: 0.00108 AC: 45 AN: 41576

American (AMR) AF: 0.00261 AC: 40 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 3 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00640 AC: 68 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00703 AC: 478 AN: 68032

Other (OTH) AF: 0.00331 AC: 7 AN: 2116

Alfa AF: 0.00513 Hom.: 0

Bravo AF: 0.00373

TwinsUK AF: 0.00728 AC: 27

ALSPAC AF: 0.00649 AC: 25

ESP6500AA AF: 0.00114 AC: 5

ESP6500EA AF: 0.00721 AC: 62

ExAC AF: 0.00385 AC: 468

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	KBG syndrome (3)
-	-	3	not provided (3)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.78
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.2
DANN	Benign	0.31
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.17	T
MetaRNN	Benign	0.0047	T
PhyloP100		0.51
GERP RS		-1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism

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: rs147328392; hg19: chr16-89354918;