10-125974366-T-C

Variant summary

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

The NM_145235.5(FANK1):c.14-5795T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 152,094 control chromosomes in the GnomAD database, including 4,429 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 0.23 (4429 hom., cov: 32)
• Consequence: FANK1 NM_145235.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.298 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FANK1	NM_145235.5	c.14-5795T>C		intron_variant		ENST00000368693.6
FANK1	NM_001350939.2	c.14-5795T>C		intron_variant
FANK1	NM_001363549.2	c.-5-5795T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FANK1	ENST00000368693.6	c.14-5795T>C		intron_variant		1	NM_145235.5	P1

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35057 AN: 151976 Hom.: 4426 Cov.: 32

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.192

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

GnomAD4 genome AF: 0.231 AC: 35076 AN: 152094 Hom.: 4429 Cov.: 32 AF XY: 0.233 AC XY: 17306 AN XY: 74336

Gnomad4 AFR AF: 0.152

Gnomad4 AMR AF: 0.216

Gnomad4 ASJ AF: 0.121

Gnomad4 EAS AF: 0.310

Gnomad4 SAS AF: 0.183

Gnomad4 FIN AF: 0.371

Gnomad4 NFE AF: 0.266

Gnomad4 OTH AF: 0.191

Alfa AF: 0.239 Hom.: 9382

Bravo AF: 0.218

Asia WGS AF: 0.243 AC: 847 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.46
Dann	Benign	0.81

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: rs7918092; hg19: chr10-127662935;