rs9294437

Positions:

• chr6-89435415-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001242809.2(ANKRD6):​c.-144+2040T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 152,138 control chromosomes in the GnomAD database, including 2,182 homozygotes. 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 0.15 (2182 hom., cov: 32)
• Consequence: ANKRD6 NM_001242809.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.924

Genes affected

ANKRD6 (HGNC:17280): (ankyrin repeat domain 6) Predicted to be involved in negative regulation of canonical Wnt signaling pathway and positive regulation of JNK cascade. Predicted to act upstream of or within positive regulation of Wnt signaling pathway, planar cell polarity pathway. Located in intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

LOC124901360 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKRD6	NM_001242809.2	c.-144+2040T>C		intron_variant		ENST00000339746.9
LOC124901360	XR_007059675.1	n.6119A>G		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKRD6	ENST00000339746.9	c.-144+2040T>C		intron_variant		1	NM_001242809.2	A1

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22365 AN: 152020 Hom.: 2176 Cov.: 32

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.0452

Gnomad EAS AF: 0.408

Gnomad SAS AF: 0.0369

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0896

Gnomad OTH AF: 0.119

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.147 AC: 22381 AN: 152138 Hom.: 2182 Cov.: 32 AF XY: 0.152 AC XY: 11295 AN XY: 74394

Gnomad4 AFR AF: 0.208

Gnomad4 AMR AF: 0.198

Gnomad4 ASJ AF: 0.0452

Gnomad4 EAS AF: 0.407

Gnomad4 SAS AF: 0.0367

Gnomad4 FIN AF: 0.177

Gnomad4 NFE AF: 0.0896

Gnomad4 OTH AF: 0.116

Alfa AF: 0.111 Hom.: 248

Bravo AF: 0.152

Asia WGS AF: 0.165 AC: 571 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.4
DANN	Benign	0.77

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: rs9294437; hg19: chr6-90145134; COSMIC: COSV60235990;