rs7186101

Variant names:

• chr16-89324569-C-T
• rs7186101
• NM_013275.6:c.-59-7491G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-89324569-C-T
• chr16-89324569-C-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_013275.6(ANKRD11):​c.-59-7491G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00721 in 454,436 control chromosomes in the GnomAD database, including 81 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.017 (66 hom., cov: 32)
  • Exomes 𝑓: 0.0022 (15 hom.)
• Consequence: ANKRD11 NM_013275.6 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.84
• Publications: 4 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

LOC128462377 (HGNC:0):

LOC128462377 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 16-89324569-C-T is Benign according to our data. Variant chr16-89324569-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 445360.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0573 is higher than 0.05.

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.-59-7491G>A		intron	N/A	NP_037407.4
	LOC128462377	NM_001416403.1	MANE Select	c.10-7494G>A		intron	N/A	NP_001403332.1	A0AAA9YHJ5
	ANKRD11	NM_001256182.2		c.-59-7491G>A		intron	N/A	NP_001243111.1	Q6UB99

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD11	ENST00000301030.10	TSL:5 MANE Select	c.-59-7491G>A		intron	N/A	ENSP00000301030.4	Q6UB99
	ENSG00000288715	ENST00000711617.1	MANE Select	c.10-7494G>A		intron	N/A	ENSP00000518812.1	A0AAA9YHJ5
	ANKRD11	ENST00000378330.7	TSL:1	c.-59-7491G>A		intron	N/A	ENSP00000367581.2	Q6UB99

Frequencies

GnomAD3 genomes AF: 0.0171 AC: 2606 AN: 152144 Hom.: 66 Cov.: 32

Gnomad AFR AF: 0.0592

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00714

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.0120

GnomAD2 exomes AF: 0.00345 AC: 436 AN: 126336 AF XY: 0.00255

Gnomad AFR exome AF: 0.0587

Gnomad AMR exome AF: 0.00268

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000129

Gnomad OTH exome AF: 0.00127

GnomAD4 exome AF: 0.00219 AC: 662 AN: 302174 Hom.: 15 Cov.: 0 AF XY: 0.00154 AC XY: 265 AN XY: 172110

African (AFR) AF: 0.0593 AC: 510 AN: 8602

American (AMR) AF: 0.00261 AC: 71 AN: 27206

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10614

East Asian (EAS) AF: 0.00 AC: 0 AN: 9198

South Asian (SAS) AF: 0.000202 AC: 12 AN: 59526

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 12292

Middle Eastern (MID) AF: 0.00181 AC: 5 AN: 2768

European-Non Finnish (NFE) AF: 0.0000950 AC: 15 AN: 157814

Other (OTH) AF: 0.00346 AC: 49 AN: 14154

GnomAD4 genome AF: 0.0172 AC: 2613 AN: 152262 Hom.: 66 Cov.: 32 AF XY: 0.0164 AC XY: 1220 AN XY: 74466

African (AFR) AF: 0.0592 AC: 2461 AN: 41542

American (AMR) AF: 0.00713 AC: 109 AN: 15290

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

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5192

South Asian (SAS) AF: 0.000830 AC: 4 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

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

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68012

Other (OTH) AF: 0.0118 AC: 25 AN: 2110

Alfa AF: 0.00251 Hom.: 2

Bravo AF: 0.0197

Asia WGS AF: 0.00462 AC: 16 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.45
DANN	Benign	0.72
PhyloP100		-1.8
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: rs7186101; hg19: chr16-89390977;