rs2102360

Positions:

• chr8-41831310-A-G

Variant summary

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

The ENST00000265709.14(ANK1):​c.126+65045T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 152,178 control chromosomes in the GnomAD database, including 1,923 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 0.15 (1923 hom., cov: 31)
• Consequence: ANK1 ENST00000265709.14 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.318

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANK1	NM_001142446.2	c.126+65045T>C		intron_variant			NP_001135918.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANK1	ENST00000265709.14	c.126+65045T>C		intron_variant		1		ENSP00000265709	P4
ANK1	ENST00000705521.1	c.126+65045T>C		intron_variant				ENSP00000516136	A2

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23215 AN: 152060 Hom.: 1922 Cov.: 31

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.0689

Gnomad EAS AF: 0.0172

Gnomad SAS AF: 0.0927

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.130

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

GnomAD4 genome AF: 0.153 AC: 23230 AN: 152178 Hom.: 1923 Cov.: 31 AF XY: 0.148 AC XY: 10991 AN XY: 74400

Gnomad4 AFR AF: 0.178

Gnomad4 AMR AF: 0.145

Gnomad4 ASJ AF: 0.0689

Gnomad4 EAS AF: 0.0170

Gnomad4 SAS AF: 0.0934

Gnomad4 FIN AF: 0.134

Gnomad4 NFE AF: 0.160

Gnomad4 OTH AF: 0.128

Alfa AF: 0.150 Hom.: 2439

Bravo AF: 0.154

Asia WGS AF: 0.0800 AC: 280 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.80
DANN	Benign	0.61

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: rs2102360; hg19: chr8-41688828;