rs847845

Positions:

• chr6-34956087-G-A
• chr6-34956087-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.198-11152G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 151,586 control chromosomes in the GnomAD database, including 6,014 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 0.24 (6014 hom., cov: 31)
• Consequence: ANKS1A NM_015245.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.822

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.466 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKS1A	NM_015245.3	c.198-11152G>A		intron_variant		ENST00000360359.5	NP_056060.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKS1A	ENST00000360359.5	c.198-11152G>A		intron_variant		1	NM_015245.3	ENSP00000353518
ANKS1A	ENST00000649117.1	c.198-11152G>A		intron_variant				ENSP00000497393	P1
ANKS1A	ENST00000650178.1	c.198-11152G>A		intron_variant				ENSP00000497939

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35781 AN: 151468 Hom.: 5994 Cov.: 31

Gnomad AFR AF: 0.472

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.247

Gnomad SAS AF: 0.246

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.240

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

GnomAD4 genome AF: 0.236 AC: 35829 AN: 151586 Hom.: 6014 Cov.: 31 AF XY: 0.237 AC XY: 17536 AN XY: 74086

Gnomad4 AFR AF: 0.472

Gnomad4 AMR AF: 0.187

Gnomad4 ASJ AF: 0.211

Gnomad4 EAS AF: 0.246

Gnomad4 SAS AF: 0.245

Gnomad4 FIN AF: 0.135

Gnomad4 NFE AF: 0.122

Gnomad4 OTH AF: 0.238

Alfa AF: 0.126 Hom.: 567

Bravo AF: 0.251

Asia WGS AF: 0.263 AC: 909 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.4
DANN	Benign	0.65

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: rs847845; hg19: chr6-34923864;