6-35067023-G-C

Position:

• chr6-35067023-G-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKS1A	NM_015245.3	c.2184+6770G>C		intron_variant		ENST00000360359.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKS1A	ENST00000360359.5	c.2184+6770G>C		intron_variant		1	NM_015245.3

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

Gnomad4 AFR AF: 0.0360

Gnomad4 AMR AF: 0.156

Gnomad4 ASJ AF: 0.0608

Gnomad4 EAS AF: 0.0166

Gnomad4 SAS AF: 0.0737

Gnomad4 FIN AF: 0.188

Gnomad4 NFE AF: 0.202

Gnomad4 OTH AF: 0.0908

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.091
DANN	Benign	0.61

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: rs17609940; hg19: chr6-35034800;