rs80051617

Variant names:

• chr16-89324500-G-A
• rs80051617
• NM_013275.6:c.-59-7422C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_013275.6(ANKRD11):​c.-59-7422C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00417 in 456,382 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0098 (19 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (6 hom.)
• Consequence: ANKRD11 NM_013275.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.365
• Publications: 1 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

LOC128462377 (HGNC:0):

LOC128462377 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 16-89324500-G-A is Benign according to our data. Variant chr16-89324500-G-A is described in ClinVar as Benign. ClinVar VariationId is 376928.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00979 (1491/152340) while in subpopulation AFR AF = 0.0345 (1433/41572). AF 95% confidence interval is 0.033. There are 19 homozygotes in GnomAd4. There are 693 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1491 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.-59-7422C>T		intron	N/A	NP_037407.4
	LOC128462377	NM_001416403.1	MANE Select	c.10-7425C>T		intron	N/A	NP_001403332.1
	ANKRD11	NM_001256182.2		c.-59-7422C>T		intron	N/A	NP_001243111.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD11	ENST00000301030.10	TSL:5 MANE Select	c.-59-7422C>T		intron	N/A	ENSP00000301030.4
	ENSG00000288715	ENST00000711617.1	MANE Select	c.10-7425C>T		intron	N/A	ENSP00000518812.1
	ANKRD11	ENST00000378330.7	TSL:1	c.-59-7422C>T		intron	N/A	ENSP00000367581.2

Frequencies

GnomAD3 genomes AF: 0.00979 AC: 1491 AN: 152222 Hom.: 19 Cov.: 32

Gnomad AFR AF: 0.0346

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00268

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00526

GnomAD2 exomes AF: 0.00238 AC: 305 AN: 128096 AF XY: 0.00187

Gnomad AFR exome AF: 0.0394

Gnomad AMR exome AF: 0.00238

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000211

Gnomad OTH exome AF: 0.00125

GnomAD4 exome AF: 0.00135 AC: 411 AN: 304042 Hom.: 6 Cov.: 0 AF XY: 0.000947 AC XY: 164 AN XY: 173114

African (AFR) AF: 0.0355 AC: 306 AN: 8622

American (AMR) AF: 0.00268 AC: 73 AN: 27276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10788

East Asian (EAS) AF: 0.00 AC: 0 AN: 9210

South Asian (SAS) AF: 0.0000335 AC: 2 AN: 59744

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 12368

Middle Eastern (MID) AF: 0.000719 AC: 2 AN: 2782

European-Non Finnish (NFE) AF: 0.0000189 AC: 3 AN: 159024

Other (OTH) AF: 0.00176 AC: 25 AN: 14228

GnomAD4 genome AF: 0.00979 AC: 1491 AN: 152340 Hom.: 19 Cov.: 32 AF XY: 0.00930 AC XY: 693 AN XY: 74502

African (AFR) AF: 0.0345 AC: 1433 AN: 41572

American (AMR) AF: 0.00268 AC: 41 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68024

Other (OTH) AF: 0.00520 AC: 11 AN: 2114

Alfa AF: 0.00608 Hom.: 1

Bravo AF: 0.0110

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.2
DANN	Benign	0.77
PhyloP100		0.36
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: rs80051617; hg19: chr16-89390908;