rs7366048

chr1-37997832-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_004468.5(FHL3):c.540G>A(p.Pro180=) 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0330

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]

ACMG classification

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	UniProt
FHL3	NM_004468.5	c.540G>A	p.Pro180=	synonymous_variant	5/6	ENST00000373016.4
FHL3	NM_001243878.2	c.216G>A	p.Pro72=	synonymous_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FHL3	ENST00000373016.4	c.540G>A	p.Pro180=	synonymous_variant	5/6	1	NM_004468.5	P1
FHL3	ENST00000485803.5	n.530G>A		non_coding_transcript_exon_variant	4/5	1
FHL3	ENST00000475084.5	n.360G>A		non_coding_transcript_exon_variant	3/4	5
FHL3	ENST00000477194.5	n.728G>A		non_coding_transcript_exon_variant	5/6	2

Frequencies

GnomAD3 genomes AF: 0.496 AC: 75295 AN: 151886 Hom.: 19632 Cov.: 32

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

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.: 61 AF XY: 0.430 AC XY: 312665 AN XY: 727204

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.: 32 AF XY: 0.497 AC XY: 36930 AN XY: 74306

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	12
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

Other links and lift over

dbSNP: rs7366048; hg19: chr1-38463504; COSMIC: COSV65952844; COSMIC: COSV65952844;