rs35489610

chrX-136151292-T-TA

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001159702.3(FHL1):c.-101+3665dup variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.69 (19068 hom., 23694 hem., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: FHL1 NM_001159702.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.183

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 Likely_benign. Variant got -4 ACMG points.

• BS2: High Homozygotes in GnomAd at 19066 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FHL1	NM_001159702.3	c.-101+3665dup		intron_variant		ENST00000394155.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FHL1	ENST00000394155.8	c.-101+3665dup		intron_variant		5	NM_001159702.3

Frequencies

GnomAD3 genomes AF: 0.690 AC: 77306 AN: 111974 Hom.: 19066 Cov.: 0 AF XY: 0.693 AC XY: 23657 AN XY: 34156

Gnomad AFR AF: 0.520

Gnomad AMI AF: 0.732

Gnomad AMR AF: 0.676

Gnomad ASJ AF: 0.680

Gnomad EAS AF: 0.616

Gnomad SAS AF: 0.665

Gnomad FIN AF: 0.823

Gnomad MID AF: 0.641

Gnomad NFE AF: 0.784

Gnomad OTH AF: 0.651

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.690 AC: 77338 AN: 112029 Hom.: 19068 Cov.: 0 AF XY: 0.692 AC XY: 23694 AN XY: 34221

Gnomad4 AFR AF: 0.521

Gnomad4 AMR AF: 0.676

Gnomad4 ASJ AF: 0.680

Gnomad4 EAS AF: 0.616

Gnomad4 SAS AF: 0.667

Gnomad4 FIN AF: 0.823

Gnomad4 NFE AF: 0.784

Gnomad4 OTH AF: 0.651

Alfa AF: 0.744 Hom.: 6123

Bravo AF: 0.673

Asia WGS AF: 0.619 AC: 1562 AN: 2522

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs35489610; hg19: chrX-135233451;