dbSNP rs7337292: FGF14:c.209-170769T>C (chr13-102046065-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000376131.9(FGF14):c.209-170769T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.473 in 154,140 control chromosomes in the GnomAD database, including 17,898 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 0.47 ( 17616 hom., cov: 32)

Exomes 𝑓: 0.51 ( 282 hom. )

Consequence

FGF14
ENST00000376131.9 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.22

Publications

6 publications found

Variant links:

Genes affected

FGF14 (HGNC:3671): (fibroblast growth factor 14) The protein encoded by this gene is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities, and are involved in a variety of biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion. A mutation in this gene is associated with autosomal dominant cerebral ataxia. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2008]

FGF14 links:

MIR4705 (HGNC:41567): (microRNA 4705) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR4705 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.707 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
FGF14	NM_175929.3 link	c.209-170769T>C	intron_variant	Intron 1 of 4	NP_787125.1	Q92915-2
FGF14	NM_001321939.2 link	c.209-177237T>C	intron_variant	Intron 1 of 3	NP_001308868.1
FGF14	NM_001321945.2 link	c.92-170769T>C	intron_variant	Intron 2 of 5	NP_001308874.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
FGF14	ENST00000376131.9 link	c.209-170769T>C	intron_variant	Intron 1 of 4	1	ENSP00000365301.3	Q92915-2
FGF14	ENST00000418923.3 link	c.92-170769T>C	intron_variant	Intron 2 of 5	3	ENSP00000516414.1	A0A9L9PXK7
FGF14	ENST00000706494.1 link	c.-59-170769T>C	intron_variant	Intron 3 of 6		ENSP00000516417.1	A0A9L9PX77

Frequencies

GnomAD3 genomes

AF:

0.472

AC:

71703

AN:

151842

Hom.:

17595

Cov.:

show subpopulations

Gnomad AFR

AF:

0.567

Gnomad AMI

AF:

0.388

Gnomad AMR

AF:

0.541

Gnomad ASJ

AF:

0.421

Gnomad EAS

AF:

0.727

Gnomad SAS

AF:

0.441

Gnomad FIN

AF:

0.338

Gnomad MID

AF:

0.491

Gnomad NFE

AF:

0.406

Gnomad OTH

AF:

0.489

GnomAD4 exome

AF:

0.507

AC:

1105

AN:

2178

Hom.:

282

AF XY:

0.494

AC XY:

535

AN XY:

1084

show subpopulations

African (AFR)

AF:

0.568

AC:

AN:

American (AMR)

AF:

0.875

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.383

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AF:

0.525

AC:

853

AN:

1626

European-Non Finnish (NFE)

AF:

0.413

AC:

AN:

184

Other (OTH)

AF:

0.473

AC:

AN:

188

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

102

128

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.472

AC:

71767

AN:

151962

Hom.:

17616

Cov.:

AF XY:

0.471

AC XY:

34980

AN XY:

74258

show subpopulations

African (AFR)

AF:

0.567

AC:

23514

AN:

41462

American (AMR)

AF:

0.541

AC:

8258

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.421

AC:

1458

AN:

3460

East Asian (EAS)

AF:

0.727

AC:

3742

AN:

5148

South Asian (SAS)

AF:

0.440

AC:

2117

AN:

4810

European-Finnish (FIN)

AF:

0.338

AC:

3575

AN:

10572

Middle Eastern (MID)

AF:

0.493

AC:

145

AN:

294

European-Non Finnish (NFE)

AF:

0.406

AC:

27576

AN:

67918

Other (OTH)

AF:

0.487

AC:

1028

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1922

3844

5765

7687

9609

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

640

1280

1920

2560

3200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.456

Hom.:

2860

Bravo

AF:

0.492

Asia WGS

AF:

0.548

AC:

1907

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.70

(source)

DANN

Benign

0.64

PhyloP100

-1.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over