rs9018

Positions:

• chrX-136210923-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001159702.3(FHL1):​c.*969G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.495 in 380,390 control chromosomes in the GnomAD database, including 30,721 homozygotes. There are 65,789 hemizygotes in GnomAD. 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 (8823 hom., 16104 hem., cov: 23)
  • Exomes 𝑓: 0.50 (21898 hom. 49685 hem.)
• Consequence: FHL1 NM_001159702.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.802

Genes affected

FHL1 (HGNC:3702): (four and a half LIM domains 1) This gene encodes a member of the four-and-a-half-LIM-only protein family. Family members contain two highly conserved, tandemly arranged, zinc finger domains with four highly conserved cysteines binding a zinc atom in each zinc finger. Expression of these family members occurs in a cell- and tissue-specific mode and these proteins are involved in many cellular processes. Mutations in this gene have been found in patients with Emery-Dreifuss muscular dystrophy. Multiple alternately spliced transcript variants which encode different protein isoforms have been described.[provided by RefSeq, Nov 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.673 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FHL1	NM_001159699.2	c.*898G>A		3_prime_UTR_variant	6/6	ENST00000370683.6
FHL1	NM_001159702.3	c.*969G>A		3_prime_UTR_variant	8/8	ENST00000394155.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FHL1	ENST00000370683.6	c.*898G>A		3_prime_UTR_variant	6/6	1	NM_001159699.2	P1
FHL1	ENST00000394155.8	c.*969G>A		3_prime_UTR_variant	8/8	5	NM_001159702.3

Frequencies

GnomAD3 genomes AF: 0.474 AC: 52758 AN: 111239 Hom.: 8821 Cov.: 23 AF XY: 0.480 AC XY: 16068 AN XY: 33457

Gnomad AFR AF: 0.386

Gnomad AMI AF: 0.479

Gnomad AMR AF: 0.476

Gnomad ASJ AF: 0.443

Gnomad EAS AF: 0.696

Gnomad SAS AF: 0.473

Gnomad FIN AF: 0.611

Gnomad MID AF: 0.343

Gnomad NFE AF: 0.498

Gnomad OTH AF: 0.431

GnomAD3 exomes AF: 0.513 AC: 48925 AN: 95413 Hom.: 8179 AF XY: 0.507 AC XY: 18053 AN XY: 35601

Gnomad AFR exome AF: 0.384

Gnomad AMR exome AF: 0.543

Gnomad ASJ exome AF: 0.435

Gnomad EAS exome AF: 0.710

Gnomad SAS exome AF: 0.477

Gnomad FIN exome AF: 0.624

Gnomad NFE exome AF: 0.489

Gnomad OTH exome AF: 0.476

GnomAD4 exome AF: 0.503 AC: 135336 AN: 269093 Hom.: 21898 Cov.: 0 AF XY: 0.501 AC XY: 49685 AN XY: 99129

Gnomad4 AFR exome AF: 0.390

Gnomad4 AMR exome AF: 0.535

Gnomad4 ASJ exome AF: 0.436

Gnomad4 EAS exome AF: 0.655

Gnomad4 SAS exome AF: 0.482

Gnomad4 FIN exome AF: 0.612

Gnomad4 NFE exome AF: 0.497

Gnomad4 OTH exome AF: 0.482

GnomAD4 genome AF: 0.474 AC: 52785 AN: 111297 Hom.: 8823 Cov.: 23 AF XY: 0.480 AC XY: 16104 AN XY: 33525

Gnomad4 AFR AF: 0.387

Gnomad4 AMR AF: 0.476

Gnomad4 ASJ AF: 0.443

Gnomad4 EAS AF: 0.696

Gnomad4 SAS AF: 0.474

Gnomad4 FIN AF: 0.611

Gnomad4 NFE AF: 0.498

Gnomad4 OTH AF: 0.434

Alfa AF: 0.492 Hom.: 9502

Bravo AF: 0.463

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.8
DANN	Benign	0.69

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: rs9018; hg19: chrX-135293082;