rs7006290

Positions:

• chr8-41757620-G-A

Variant summary

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

The NM_000037.4(ANK1):​c.129+416C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 152,050 control chromosomes in the GnomAD database, including 7,384 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 (7384 hom., cov: 33)
• Consequence: ANK1 NM_000037.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19

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 (SAS) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANK1	NM_000037.4	c.129+416C>T		intron_variant		ENST00000289734.13	NP_000028.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANK1	ENST00000289734.13	c.129+416C>T		intron_variant		1	NM_000037.4	ENSP00000289734	A2

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46699 AN: 151932 Hom.: 7376 Cov.: 33

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.406

Gnomad AMR AF: 0.259

Gnomad ASJ AF: 0.434

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.318

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

GnomAD4 genome AF: 0.307 AC: 46733 AN: 152050 Hom.: 7384 Cov.: 33 AF XY: 0.311 AC XY: 23093 AN XY: 74330

Gnomad4 AFR AF: 0.271

Gnomad4 AMR AF: 0.259

Gnomad4 ASJ AF: 0.434

Gnomad4 EAS AF: 0.206

Gnomad4 SAS AF: 0.348

Gnomad4 FIN AF: 0.430

Gnomad4 NFE AF: 0.317

Gnomad4 OTH AF: 0.321

Alfa AF: 0.324 Hom.: 8586

Bravo AF: 0.290

Asia WGS AF: 0.314 AC: 1089 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	0.092
DANN	Benign	0.75

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: rs7006290; hg19: chr8-41615138;