6-35067023-G-C

Variant names:

• chr6-35067023-G-C
• rs17609940
• NM_015245.3:c.2184+6770G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015245.3(ANKS1A):​c.2184+6770G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 152,216 control chromosomes in the GnomAD database, including 1,876 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 0.14 (1876 hom., cov: 32)
• Consequence: ANKS1A NM_015245.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.69
• Publications: 84 publications found

Genes affected

ANKS1A (HGNC:20961): (ankyrin repeat and sterile alpha motif domain containing 1A) Predicted to enable ephrin receptor binding activity. Predicted to be involved in ephrin receptor signaling pathway; neuron remodeling; and substrate-dependent cell migration. Predicted to act upstream of or within negative regulation of ubiquitin-dependent protein catabolic process and regulation of ephrin receptor signaling pathway. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000299947 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015245.3. 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
	ANKS1A	NM_015245.3	MANE Select	c.2184+6770G>C		intron	N/A	NP_056060.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKS1A	ENST00000360359.5	TSL:1 MANE Select	c.2184+6770G>C		intron	N/A	ENSP00000353518.3
	ANKS1A	ENST00000649117.1		c.2247+6770G>C		intron	N/A	ENSP00000497393.1
	ANKS1A	ENST00000922348.1		c.2184+6770G>C		intron	N/A	ENSP00000592407.1

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20563 AN: 152098 Hom.: 1874 Cov.: 32

Gnomad AFR AF: 0.0361

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.0608

Gnomad EAS AF: 0.0162

Gnomad SAS AF: 0.0736

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.0913

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

GnomAD4 genome AF: 0.135 AC: 20564 AN: 152216 Hom.: 1876 Cov.: 32 AF XY: 0.131 AC XY: 9762 AN XY: 74424

African (AFR) AF: 0.0360 AC: 1496 AN: 41548

American (AMR) AF: 0.156 AC: 2383 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0608 AC: 211 AN: 3472

East Asian (EAS) AF: 0.0166 AC: 86 AN: 5182

South Asian (SAS) AF: 0.0737 AC: 355 AN: 4820

European-Finnish (FIN) AF: 0.188 AC: 1995 AN: 10588

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.202 AC: 13706 AN: 67992

Other (OTH) AF: 0.0908 AC: 192 AN: 2114

Alfa AF: 0.101 Hom.: 168

Bravo AF: 0.128

Asia WGS AF: 0.0490 AC: 175 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.091
DANN	Benign	0.61
PhyloP100		-2.7
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: rs17609940; hg19: chr6-35034800;