rs4420176

Positions:

• chr10-125987629-C-T

Variant summary

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

The NM_145235.5(FANK1):​c.192-922C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 151,804 control chromosomes in the GnomAD database, including 9,618 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 0.34 (9618 hom., cov: 32)
• Consequence: FANK1 NM_145235.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.50

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) 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.192-922C>T		intron_variant		ENST00000368693.6	NP_660278.3
FANK1	NM_001350939.2	c.192-922C>T		intron_variant			NP_001337868.1
FANK1	NM_001363549.2	c.174-922C>T		intron_variant			NP_001350478.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FANK1	ENST00000368693.6	c.192-922C>T		intron_variant		1	NM_145235.5	ENSP00000357682.1

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52201 AN: 151686 Hom.: 9607 Cov.: 32

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.297

Gnomad ASJ AF: 0.474

Gnomad EAS AF: 0.330

Gnomad SAS AF: 0.450

Gnomad FIN AF: 0.339

Gnomad MID AF: 0.338

Gnomad NFE AF: 0.414

Gnomad OTH AF: 0.363

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

GnomAD4 genome AF: 0.344 AC: 52229 AN: 151804 Hom.: 9618 Cov.: 32 AF XY: 0.341 AC XY: 25289 AN XY: 74168

Gnomad4 AFR AF: 0.223

Gnomad4 AMR AF: 0.296

Gnomad4 ASJ AF: 0.474

Gnomad4 EAS AF: 0.330

Gnomad4 SAS AF: 0.452

Gnomad4 FIN AF: 0.339

Gnomad4 NFE AF: 0.414

Gnomad4 OTH AF: 0.367

Alfa AF: 0.366 Hom.: 1792

Bravo AF: 0.332

Asia WGS AF: 0.380 AC: 1323 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	0.36
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: rs4420176; hg19: chr10-127676198;