chr6-35007638-T-C

Variant names:

• chr6-35007638-T-C
• rs2140418
• NM_015245.3:c.1424-9835T>C

Variant summary

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

The NM_015245.3(ANKS1A):​c.1424-9835T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.674 in 152,136 control chromosomes in the GnomAD database, including 36,529 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 0.67 (36529 hom., cov: 32)
• Consequence: ANKS1A NM_015245.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.754

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=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.793 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKS1A	NM_015245.3	c.1424-9835T>C		intron_variant	Intron 10 of 23	ENST00000360359.5	NP_056060.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKS1A	ENST00000360359.5	c.1424-9835T>C		intron_variant	Intron 10 of 23	1	NM_015245.3	ENSP00000353518.3
ANKS1A	ENST00000649117.1	c.1487-9835T>C		intron_variant	Intron 11 of 24			ENSP00000497393.1

Frequencies

GnomAD3 genomes AF: 0.674 AC: 102463 AN: 152018 Hom.: 36506 Cov.: 32

Gnomad AFR AF: 0.452

Gnomad AMI AF: 0.938

Gnomad AMR AF: 0.711

Gnomad ASJ AF: 0.671

Gnomad EAS AF: 0.416

Gnomad SAS AF: 0.647

Gnomad FIN AF: 0.805

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.799

Gnomad OTH AF: 0.660

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

GnomAD4 genome AF: 0.674 AC: 102525 AN: 152136 Hom.: 36529 Cov.: 32 AF XY: 0.673 AC XY: 50043 AN XY: 74374

Gnomad4 AFR AF: 0.452

Gnomad4 AMR AF: 0.711

Gnomad4 ASJ AF: 0.671

Gnomad4 EAS AF: 0.417

Gnomad4 SAS AF: 0.647

Gnomad4 FIN AF: 0.805

Gnomad4 NFE AF: 0.799

Gnomad4 OTH AF: 0.661

Alfa AF: 0.767 Hom.: 71990

Bravo AF: 0.656

Asia WGS AF: 0.563 AC: 1958 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	5.6
DANN	Benign	0.82

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: rs2140418; hg19: chr6-34975415;