10-125974366-T-C

Variant names:

• chr10-125974366-T-C
• rs7918092
• NM_145235.5:c.14-5795T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145235.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FANK1	NM_145235.5	MANE Select	c.14-5795T>C		intron	N/A	NP_660278.3
	FANK1	NM_001350939.2		c.14-5795T>C		intron	N/A	NP_001337868.1	Q8TC84-3
	FANK1	NM_001363549.2		c.-5-5795T>C		intron	N/A	NP_001350478.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FANK1	ENST00000368693.6	TSL:1 MANE Select	c.14-5795T>C		intron	N/A	ENSP00000357682.1	Q8TC84-1
	FANK1	ENST00000916275.1		c.14-5795T>C		intron	N/A	ENSP00000586334.1
	FANK1	ENST00000902356.1		c.14-5795T>C		intron	N/A	ENSP00000572415.1

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

African (AFR) AF: 0.152 AC: 6313 AN: 41492

American (AMR) AF: 0.216 AC: 3299 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 418 AN: 3466

East Asian (EAS) AF: 0.310 AC: 1600 AN: 5154

South Asian (SAS) AF: 0.183 AC: 881 AN: 4822

European-Finnish (FIN) AF: 0.371 AC: 3923 AN: 10584

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.266 AC: 18078 AN: 67976

Other (OTH) AF: 0.191 AC: 404 AN: 2110

Alfa AF: 0.242 Hom.: 19804

Bravo AF: 0.218

Asia WGS AF: 0.243 AC: 847 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.46
DANN	Benign	0.81
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7918092; hg19: chr10-127662935;