chr6-35072643-T-C

Position:

• chr6-35072643-T-C

Variant summary

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

The NM_015245.3(ANKS1A):​c.2185-5915T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.8 in 152,168 control chromosomes in the GnomAD database, including 49,711 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 0.80 (49711 hom., cov: 33)
• Consequence: ANKS1A NM_015245.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.368

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=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.895 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKS1A	NM_015245.3	c.2185-5915T>C		intron_variant		ENST00000360359.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKS1A	ENST00000360359.5	c.2185-5915T>C		intron_variant		1	NM_015245.3

Frequencies

GnomAD3 genomes AF: 0.800 AC: 121694 AN: 152050 Hom.: 49679 Cov.: 33

Gnomad AFR AF: 0.639

Gnomad AMI AF: 0.928

Gnomad AMR AF: 0.845

Gnomad ASJ AF: 0.692

Gnomad EAS AF: 0.896

Gnomad SAS AF: 0.918

Gnomad FIN AF: 0.938

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.856

Gnomad OTH AF: 0.781

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

GnomAD4 genome AF: 0.800 AC: 121779 AN: 152168 Hom.: 49711 Cov.: 33 AF XY: 0.807 AC XY: 60044 AN XY: 74400

Gnomad4 AFR AF: 0.639

Gnomad4 AMR AF: 0.846

Gnomad4 ASJ AF: 0.692

Gnomad4 EAS AF: 0.896

Gnomad4 SAS AF: 0.918

Gnomad4 FIN AF: 0.938

Gnomad4 NFE AF: 0.856

Gnomad4 OTH AF: 0.783

Alfa AF: 0.844 Hom.: 49984

Bravo AF: 0.783

Asia WGS AF: 0.891 AC: 3095 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.4
DANN	Benign	0.34

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: rs820065; hg19: chr6-35040420;