6-34938391-T-C

Variant names:

• chr6-34938391-T-C
• rs847848
• NM_015245.3:c.198-28848T>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.198-28848T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 152,104 control chromosomes in the GnomAD database, including 10,207 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 0.31 (10207 hom., cov: 32)
• Consequence: ANKS1A NM_015245.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.20
• Publications: 8 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.585 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKS1A	NM_015245.3	c.198-28848T>C		intron_variant	Intron 1 of 23	ENST00000360359.5	NP_056060.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKS1A	ENST00000360359.5	c.198-28848T>C		intron_variant	Intron 1 of 23	1	NM_015245.3	ENSP00000353518.3
ANKS1A	ENST00000649117.1	c.198-28848T>C		intron_variant	Intron 1 of 24			ENSP00000497393.1
ANKS1A	ENST00000650178.1	c.198-28848T>C		intron_variant	Intron 1 of 9			ENSP00000497939.1

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46904 AN: 151986 Hom.: 10189 Cov.: 32

Gnomad AFR AF: 0.591

Gnomad AMI AF: 0.0429

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.587

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.320

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

GnomAD4 genome AF: 0.309 AC: 46960 AN: 152104 Hom.: 10207 Cov.: 32 AF XY: 0.308 AC XY: 22901 AN XY: 74354

African (AFR) AF: 0.591 AC: 24494 AN: 41450

American (AMR) AF: 0.268 AC: 4091 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 1018 AN: 3472

East Asian (EAS) AF: 0.587 AC: 3022 AN: 5152

South Asian (SAS) AF: 0.301 AC: 1451 AN: 4824

European-Finnish (FIN) AF: 0.146 AC: 1548 AN: 10604

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.155 AC: 10538 AN: 68002

Other (OTH) AF: 0.319 AC: 674 AN: 2114

Alfa AF: 0.206 Hom.: 18135

Bravo AF: 0.331

Asia WGS AF: 0.413 AC: 1434 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.43
DANN	Benign	0.67
PhyloP100		-2.2
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: rs847848; hg19: chr6-34906168;