rs1737727

Variant names:

• chr6-34936711-T-C
• rs1737727
• NM_015245.3:c.198-30528T>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.198-30528T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 152,062 control chromosomes in the GnomAD database, including 11,076 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 0.34 (11076 hom., cov: 32)
• Consequence: ANKS1A NM_015245.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0990
• Publications: 13 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKS1A	NM_015245.3	c.198-30528T>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.198-30528T>C		intron_variant	Intron 1 of 23	1	NM_015245.3	ENSP00000353518.3
ANKS1A	ENST00000649117.1	c.198-30528T>C		intron_variant	Intron 1 of 24			ENSP00000497393.1
ANKS1A	ENST00000650178.1	c.198-30528T>C		intron_variant	Intron 1 of 9			ENSP00000497939.1

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51333 AN: 151944 Hom.: 11058 Cov.: 32

Gnomad AFR AF: 0.588

Gnomad AMI AF: 0.0626

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.334

Gnomad EAS AF: 0.590

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.347

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

GnomAD4 genome AF: 0.338 AC: 51394 AN: 152062 Hom.: 11076 Cov.: 32 AF XY: 0.339 AC XY: 25185 AN XY: 74340

African (AFR) AF: 0.588 AC: 24348 AN: 41416

American (AMR) AF: 0.292 AC: 4468 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.334 AC: 1156 AN: 3466

East Asian (EAS) AF: 0.590 AC: 3047 AN: 5168

South Asian (SAS) AF: 0.356 AC: 1716 AN: 4822

European-Finnish (FIN) AF: 0.195 AC: 2064 AN: 10600

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.202 AC: 13716 AN: 67986

Other (OTH) AF: 0.345 AC: 730 AN: 2114

Alfa AF: 0.255 Hom.: 18511

Bravo AF: 0.357

Asia WGS AF: 0.443 AC: 1540 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.1
DANN	Benign	0.71
PhyloP100		-0.099
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: rs1737727; hg19: chr6-34904488;