chr8-41713915-C-T

Position:

• chr8-41713915-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000037.4(ANK1):​c.1800+241G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 152,056 control chromosomes in the GnomAD database, including 8,634 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.31 (8634 hom., cov: 33)
• Consequence: ANK1 NM_000037.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.255

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 8-41713915-C-T is Benign according to our data. Variant chr8-41713915-C-T is described in ClinVar as [Benign]. Clinvar id is 1282486.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.63 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANK1	NM_000037.4	c.1800+241G>A		intron_variant		ENST00000289734.13	NP_000028.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANK1	ENST00000289734.13	c.1800+241G>A		intron_variant		1	NM_000037.4	ENSP00000289734	A2

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47831 AN: 151938 Hom.: 8631 Cov.: 33

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.400

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.648

Gnomad SAS AF: 0.359

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.357

Gnomad OTH AF: 0.337

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

GnomAD4 genome AF: 0.315 AC: 47846 AN: 152056 Hom.: 8634 Cov.: 33 AF XY: 0.323 AC XY: 24027 AN XY: 74312

Gnomad4 AFR AF: 0.154

Gnomad4 AMR AF: 0.400

Gnomad4 ASJ AF: 0.253

Gnomad4 EAS AF: 0.648

Gnomad4 SAS AF: 0.358

Gnomad4 FIN AF: 0.370

Gnomad4 NFE AF: 0.357

Gnomad4 OTH AF: 0.335

Alfa AF: 0.339 Hom.: 5096

Bravo AF: 0.313

Asia WGS AF: 0.428 AC: 1488 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.5
DANN	Benign	0.66

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: rs558889; hg19: chr8-41571433;