1-37997832-C-T

Variant names:

• chr1-37997832-C-T
• rs7366048
• NM_004468.5:c.540G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0330
• Publications: 46 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004468.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FHL3	NM_004468.5	MANE Select	c.540G>A	p.Pro180Pro	synonymous	Exon 5 of 6	NP_004459.2
	FHL3	NM_001243878.2		c.216G>A	p.Pro72Pro	synonymous	Exon 4 of 5	NP_001230807.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FHL3	ENST00000373016.4	TSL:1 MANE Select	c.540G>A	p.Pro180Pro	synonymous	Exon 5 of 6	ENSP00000362107.3
	FHL3	ENST00000485803.5	TSL:1	n.530G>A		non_coding_transcript_exon	Exon 4 of 5
	FHL3	ENST00000850578.1		c.540G>A	p.Pro180Pro	synonymous	Exon 5 of 6	ENSP00000520866.1

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

GnomAD2 exomes AF: 0.474 AC: 119195 AN: 251274 AF XY: 0.469

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 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

African (AFR) AF: 0.655 AC: 21922 AN: 33478

American (AMR) AF: 0.540 AC: 24150 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.402 AC: 10497 AN: 26128

East Asian (EAS) AF: 0.612 AC: 24311 AN: 39700

South Asian (SAS) AF: 0.514 AC: 44321 AN: 86254

European-Finnish (FIN) AF: 0.384 AC: 20531 AN: 53412

Middle Eastern (MID) AF: 0.482 AC: 2778 AN: 5766

European-Non Finnish (NFE) AF: 0.405 AC: 450127 AN: 1111930

Other (OTH) AF: 0.458 AC: 27678 AN: 60386

GnomAD4 genome AF: 0.496 AC: 75382 AN: 152004 Hom.: 19661 Cov.: 32 AF XY: 0.497 AC XY: 36930 AN XY: 74306

African (AFR) AF: 0.644 AC: 26686 AN: 41436

American (AMR) AF: 0.523 AC: 7987 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.407 AC: 1410 AN: 3468

East Asian (EAS) AF: 0.651 AC: 3362 AN: 5162

South Asian (SAS) AF: 0.516 AC: 2489 AN: 4824

European-Finnish (FIN) AF: 0.390 AC: 4126 AN: 10574

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.406 AC: 27587 AN: 67942

Other (OTH) AF: 0.486 AC: 1025 AN: 2110

Alfa AF: 0.443 Hom.: 24247

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	12
DANN	Benign	0.63
PhyloP100		-0.033
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: rs7366048; hg19: chr1-38463504; COSMIC: COSV65952844; COSMIC: COSV65952844;