rs9294437

Variant names:

• chr6-89435415-T-C
• rs9294437
• NM_001242809.2:c.-144+2040T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001242809.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD6	NM_001242809.2	MANE Select	c.-144+2040T>C		intron	N/A	NP_001229738.1
	ANKRD6	NM_014942.4		c.-144+2040T>C		intron	N/A	NP_055757.3
	ANKRD6	NM_001242813.1		c.-144+2040T>C		intron	N/A	NP_001229742.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD6	ENST00000339746.9	TSL:1 MANE Select	c.-144+2040T>C		intron	N/A	ENSP00000345767.4
	ANKRD6	ENST00000447838.6	TSL:1	c.-144+2040T>C		intron	N/A	ENSP00000396771.2
	ANKRD6	ENST00000369408.9	TSL:1	c.-144+2040T>C		intron	N/A	ENSP00000358416.5

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

African (AFR) AF: 0.208 AC: 8621 AN: 41476

American (AMR) AF: 0.198 AC: 3030 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0452 AC: 157 AN: 3470

East Asian (EAS) AF: 0.407 AC: 2108 AN: 5178

South Asian (SAS) AF: 0.0367 AC: 177 AN: 4826

European-Finnish (FIN) AF: 0.177 AC: 1869 AN: 10588

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0896 AC: 6095 AN: 68002

Other (OTH) AF: 0.116 AC: 246 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.4
DANN	Benign	0.77
PhyloP100		-0.92
Mutation Taster		=100/0	polymorphism (auto)

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