rs147430058

Positions:

• chr16-89324332-C-A
• chr16-89324332-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_013275.6(ANKRD11):​c.-59-7254G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000225 in 1,199,336 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00023 (0 hom.)
• Consequence: ANKRD11 NM_013275.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.281

Genes affected

LOC128462377 (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BS2: High AC in GnomAd4 at 30 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC128462377	NM_001416403.1	c.10-7257G>T		intron_variant		ENST00000711617.1
ANKRD11	NM_013275.6	c.-59-7254G>T		intron_variant		ENST00000301030.10
LOC100287036	NR_168302.1	n.1263C>A		non_coding_transcript_exon_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKRD11	ENST00000301030.10	c.-59-7254G>T		intron_variant		5	NM_013275.6	P1
	ENST00000711617.1	c.10-7257G>T		intron_variant			NM_001416403.1	A2
	ENST00000562995.1	n.427C>A		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes AF: 0.000197 AC: 30 AN: 152148 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000367

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000221 AC: 28 AN: 126438 Hom.: 0 AF XY: 0.000275 AC XY: 19 AN XY: 69192

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000191

Gnomad NFE exome AF: 0.000558

Gnomad OTH exome AF: 0.000252

GnomAD4 exome AF: 0.000229 AC: 240 AN: 1047188 Hom.: 0 Cov.: 15 AF XY: 0.000234 AC XY: 121 AN XY: 517560

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000798

Gnomad4 NFE exome AF: 0.000278

Gnomad4 OTH exome AF: 0.000156

GnomAD4 genome AF: 0.000197 AC: 30 AN: 152148 Hom.: 0 Cov.: 33 AF XY: 0.000229 AC XY: 17 AN XY: 74314

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000377

Gnomad4 NFE AF: 0.000367

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000859 Hom.: 0

Bravo AF: 0.000181

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.47
DANN	Benign	0.84
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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

Other links and lift over

dbSNP: rs147430058; hg19: chr16-89390740;