Variant 11-61796827-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004111.6(FEN1):c.*323G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 301,298 control chromosomes in the GnomAD database, including 18,410 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 0.30 ( 8648 hom., cov: 32)

Exomes 𝑓: 0.34 ( 9762 hom. )

Consequence

FEN1
NM_004111.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.32

Variant links:

Genes affected

FEN1 (HGNC:3650): (flap structure-specific endonuclease 1) The protein encoded by this gene removes 5' overhanging flaps in DNA repair and processes the 5' ends of Okazaki fragments in lagging strand DNA synthesis. Direct physical interaction between this protein and AP endonuclease 1 during long-patch base excision repair provides coordinated loading of the proteins onto the substrate, thus passing the substrate from one enzyme to another. The protein is a member of the XPG/RAD2 endonuclease family and is one of ten proteins essential for cell-free DNA replication. DNA secondary structure can inhibit flap processing at certain trinucleotide repeats in a length-dependent manner by concealing the 5' end of the flap that is necessary for both binding and cleavage by the protein encoded by this gene. Therefore, secondary structure can deter the protective function of this protein, leading to site-specific trinucleotide expansions. [provided by RefSeq, Jul 2008]

FEN1 links:

FADS2 (HGNC:):

FADS2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FEN1	NM_004111.6 linkuse as main transcript	c.*323G>T		3_prime_UTR_variant	2/2	ENST00000305885.3	NP_004102.1	P39748-1Q6FHX6

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
FEN1	ENST00000305885.3 linkuse as main transcript	c.*323G>T	3_prime_UTR_variant	2/2	1	NM_004111.6	ENSP00000305480.2	P39748-1
FEN1	ENST00000535307.1 linkuse as main transcript	c.457-95G>T	intron_variant		2		ENSP00000460402.1	I3L3E9
FADS2	ENST00000574708.5 linkuse as main transcript	n.49+3799G>T	intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.296

AC:

45062

AN:

152022

Hom.:

8626

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0807

Gnomad AMI

AF:

0.253

Gnomad AMR

AF:

0.489

Gnomad ASJ

AF:

0.291

Gnomad EAS

AF:

0.554

Gnomad SAS

AF:

0.184

Gnomad FIN

AF:

0.449

Gnomad MID

AF:

0.342

Gnomad NFE

AF:

0.349

Gnomad OTH

AF:

0.342

GnomAD4 exome

AF:

0.339

AC:

50509

AN:

149158

Hom.:

9762

Cov.:

AF XY:

0.326

AC XY:

25423

AN XY:

77996

show subpopulations

Gnomad4 AFR exome

AF:

0.0672

Gnomad4 AMR exome

AF:

0.582

Gnomad4 ASJ exome

AF:

0.271

Gnomad4 EAS exome

AF:

0.440

Gnomad4 SAS exome

AF:

0.172

Gnomad4 FIN exome

AF:

0.450

Gnomad4 NFE exome

AF:

0.341

Gnomad4 OTH exome

AF:

0.344

GnomAD4 genome

AF:

0.296

AC:

45095

AN:

152140

Hom.:

8648

Cov.:

AF XY:

0.303

AC XY:

22536

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.0805

Gnomad4 AMR

AF:

0.490

Gnomad4 ASJ

AF:

0.291

Gnomad4 EAS

AF:

0.553

Gnomad4 SAS

AF:

0.186

Gnomad4 FIN

AF:

0.449

Gnomad4 NFE

AF:

0.349

Gnomad4 OTH

AF:

0.345

Alfa

AF:

0.259

Hom.:

1909

Bravo

AF:

0.296

Asia WGS

AF:

0.377

AC:

1310

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

DANN

Benign

0.82

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over