rs10090395

Variant names:

• chr8-41809356-T-C
• rs10090395
• ENST00000265709.14:c.127-51219A>G

Variant summary

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

The NM_001142446.2(ANK1):​c.127-51219A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 152,156 control chromosomes in the GnomAD database, including 7,011 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 0.29 (7011 hom., cov: 33)
• Consequence: ANK1 NM_001142446.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36

Genes affected

ANK1 (HGNC:492): (ankyrin 1) Ankyrins are a family of proteins that link the integral membrane proteins to the underlying spectrin-actin cytoskeleton and play key roles in activities such as cell motility, activation, proliferation, contact and the maintenance of specialized membrane domains. Multiple isoforms of ankyrin with different affinities for various target proteins are expressed in a tissue-specific, developmentally regulated manner. Most ankyrins are typically composed of three structural domains: an amino-terminal domain containing multiple ankyrin repeats; a central region with a highly conserved spectrin binding domain; and a carboxy-terminal regulatory domain which is the least conserved and subject to variation. Ankyrin 1, the prototype of this family, was first discovered in the erythrocytes, but since has also been found in brain and muscles. Mutations in erythrocytic ankyrin 1 have been associated in approximately half of all patients with hereditary spherocytosis. Complex patterns of alternative splicing in the regulatory domain, giving rise to different isoforms of ankyrin 1 have been described. Truncated muscle-specific isoforms of ankyrin 1 resulting from usage of an alternate promoter have also been identified. [provided by RefSeq, Dec 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANK1	NM_001142446.2	c.127-51219A>G		intron_variant	Intron 1 of 42		NP_001135918.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANK1	ENST00000265709.14	c.127-51219A>G		intron_variant	Intron 1 of 42	1		ENSP00000265709.8
ANK1	ENST00000705521.1	c.127-51219A>G		intron_variant	Intron 1 of 44			ENSP00000516136.1

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44549 AN: 152036 Hom.: 7003 Cov.: 33

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.426

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.433

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.342

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

GnomAD4 genome AF: 0.293 AC: 44560 AN: 152156 Hom.: 7011 Cov.: 33 AF XY: 0.291 AC XY: 21621 AN XY: 74386

Gnomad4 AFR AF: 0.210

Gnomad4 AMR AF: 0.426

Gnomad4 ASJ AF: 0.361

Gnomad4 EAS AF: 0.116

Gnomad4 SAS AF: 0.378

Gnomad4 FIN AF: 0.215

Gnomad4 NFE AF: 0.327

Gnomad4 OTH AF: 0.342

Alfa AF: 0.316 Hom.: 2112

Bravo AF: 0.306

Asia WGS AF: 0.249 AC: 865 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.058
DANN	Benign	0.30

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: rs10090395; hg19: chr8-41666874;