Variant rs7366048 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_004468.5(FHL3):c.540G>A(p.Pro180Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 1,613,766 control chromosomes in the GnomAD database, including 157,238 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 0.50 ( 19661 hom., cov: 32)

Exomes 𝑓: 0.43 ( 137577 hom. )

Consequence

FHL3
NM_004468.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0330

Variant links:

Genes affected

FHL3 (HGNC:3704): (four and a half LIM domains 3) The protein encoded by this gene is a member of a family of proteins containing a four-and-a-half LIM domain, which is a highly conserved double zinc finger motif. The encoded protein has been shown to interact with the cancer developmental regulators SMAD2, SMAD3, and SMAD4, the skeletal muscle myogenesis protein MyoD, and the high-affinity IgE beta chain regulator MZF-1. This protein may be involved in tumor suppression, repression of MyoD expression, and repression of IgE receptor expression. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

FHL3 links:

FHL3 (HGNC:):

FHL3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP7

Synonymous conserved (PhyloP=-0.033 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FHL3	NM_004468.5 linkuse as main transcript	c.540G>A	p.Pro180Pro	synonymous_variant	5/6	ENST00000373016.4	NP_004459.2	Q13643
FHL3	NM_001243878.2 linkuse as main transcript	c.216G>A	p.Pro72Pro	synonymous_variant	4/5		NP_001230807.1	Q13643Q96C98

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
FHL3	ENST00000373016.4 linkuse as main transcript	c.540G>A	p.Pro180Pro	synonymous_variant	5/6	1	NM_004468.5	ENSP00000362107.3	Q13643
FHL3	ENST00000485803.5 linkuse as main transcript	n.530G>A		non_coding_transcript_exon_variant	4/5	1
FHL3	ENST00000475084.5 linkuse as main transcript	n.360G>A		non_coding_transcript_exon_variant	3/4	5
FHL3	ENST00000477194.5 linkuse as main transcript	n.728G>A		non_coding_transcript_exon_variant	5/6	2

Frequencies

GnomAD3 genomes

AF:

0.496

AC:

75295

AN:

151886

Hom.:

19632

Cov.:

show subpopulations

Gnomad AFR

AF:

0.644

Gnomad AMI

AF:

0.624

Gnomad AMR

AF:

0.523

Gnomad ASJ

AF:

0.407

Gnomad EAS

AF:

0.651

Gnomad SAS

AF:

0.517

Gnomad FIN

AF:

0.390

Gnomad MID

AF:

0.456

Gnomad NFE

AF:

0.406

Gnomad OTH

AF:

0.480

GnomAD3 exomes

AF:

0.474

AC:

119195

AN:

251274

Hom.:

29454

AF XY:

0.469

AC XY:

63670

AN XY:

135814

show subpopulations

Gnomad AFR exome

AF:

0.646

Gnomad AMR exome

AF:

0.544

Gnomad ASJ exome

AF:

0.403

Gnomad EAS exome

AF:

0.666

Gnomad SAS exome

AF:

0.516

Gnomad FIN exome

AF:

0.390

Gnomad NFE exome

AF:

0.410

Gnomad OTH exome

AF:

0.456

GnomAD4 exome

AF:

0.428

AC:

626315

AN:

1461762

Hom.:

137577

Cov.:

AF XY:

0.430

AC XY:

312665

AN XY:

727204

show subpopulations

Gnomad4 AFR exome

AF:

0.655

Gnomad4 AMR exome

AF:

0.540

Gnomad4 ASJ exome

AF:

0.402

Gnomad4 EAS exome

AF:

0.612

Gnomad4 SAS exome

AF:

0.514

Gnomad4 FIN exome

AF:

0.384

Gnomad4 NFE exome

AF:

0.405

Gnomad4 OTH exome

AF:

0.458

GnomAD4 genome

AF:

0.496

AC:

75382

AN:

152004

Hom.:

19661

Cov.:

AF XY:

0.497

AC XY:

36930

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.644

Gnomad4 AMR

AF:

0.523

Gnomad4 ASJ

AF:

0.407

Gnomad4 EAS

AF:

0.651

Gnomad4 SAS

AF:

0.516

Gnomad4 FIN

AF:

0.390

Gnomad4 NFE

AF:

0.406

Gnomad4 OTH

AF:

0.486

Alfa

AF:

0.434

Hom.:

18979

Bravo

AF:

0.518

Asia WGS

AF:

0.559

AC:

1943

AN:

3478

EpiCase

AF:

0.414

EpiControl

AF:

0.414

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.63

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