rs4403725

Positions:

• chr10-125953707-A-G
• chr10-125953707-A-T

Variant summary

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

The NM_145235.5(FANK1):​c.14-26454A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 151,938 control chromosomes in the GnomAD database, including 11,639 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 0.39 (11639 hom., cov: 31)
• Consequence: FANK1 NM_145235.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.190

Genes affected

FANK1 (HGNC:23527): (fibronectin type III and ankyrin repeat domains 1) Involved in regulation of apoptotic process and regulation of transcription, DNA-templated. Located in cytosol and nucleoplasm. Colocalizes with chromatin. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FANK1	NM_145235.5	c.14-26454A>G		intron_variant		ENST00000368693.6	NP_660278.3
FANK1	NM_001350939.2	c.14-26454A>G		intron_variant			NP_001337868.1
FANK1	NM_001363549.2	c.-5-26454A>G		intron_variant			NP_001350478.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FANK1	ENST00000368693.6	c.14-26454A>G		intron_variant		1	NM_145235.5	ENSP00000357682	P1

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58571 AN: 151820 Hom.: 11624 Cov.: 31

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.436

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.265

Gnomad SAS AF: 0.424

Gnomad FIN AF: 0.423

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.440

Gnomad OTH AF: 0.369

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

GnomAD4 genome AF: 0.386 AC: 58622 AN: 151938 Hom.: 11639 Cov.: 31 AF XY: 0.383 AC XY: 28450 AN XY: 74242

Gnomad4 AFR AF: 0.333

Gnomad4 AMR AF: 0.295

Gnomad4 ASJ AF: 0.374

Gnomad4 EAS AF: 0.265

Gnomad4 SAS AF: 0.425

Gnomad4 FIN AF: 0.423

Gnomad4 NFE AF: 0.440

Gnomad4 OTH AF: 0.373

Alfa AF: 0.424 Hom.: 6538

Bravo AF: 0.368

Asia WGS AF: 0.356 AC: 1240 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	9.2
DANN	Benign	0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4403725; hg19: chr10-127642276;