rs2180062

Positions:

• chrX-136149229-T-C
• chrX-136149229-T-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001159702.3(FHL1):​c.-101+1601T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.64 (17272 hom., 21370 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: FHL1 NM_001159702.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.542

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.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FHL1	NM_001159702.3	c.-101+1601T>C		intron_variant		ENST00000394155.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FHL1	ENST00000394155.8	c.-101+1601T>C		intron_variant		5	NM_001159702.3

Frequencies

GnomAD3 genomes AF: 0.641 AC: 71009 AN: 110859 Hom.: 17275 Cov.: 23 AF XY: 0.645 AC XY: 21351 AN XY: 33109

Gnomad AFR AF: 0.352

Gnomad AMI AF: 0.733

Gnomad AMR AF: 0.653

Gnomad ASJ AF: 0.679

Gnomad EAS AF: 0.614

Gnomad SAS AF: 0.659

Gnomad FIN AF: 0.824

Gnomad MID AF: 0.654

Gnomad NFE AF: 0.783

Gnomad OTH AF: 0.611

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: 0.640 AC: 71016 AN: 110914 Hom.: 17272 Cov.: 23 AF XY: 0.644 AC XY: 21370 AN XY: 33174

Gnomad4 AFR AF: 0.352

Gnomad4 AMR AF: 0.653

Gnomad4 ASJ AF: 0.679

Gnomad4 EAS AF: 0.613

Gnomad4 SAS AF: 0.661

Gnomad4 FIN AF: 0.824

Gnomad4 NFE AF: 0.783

Gnomad4 OTH AF: 0.611

Alfa AF: 0.717 Hom.: 5887

Bravo AF: 0.615

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.4
DANN	Benign	0.65

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2180062; hg19: chrX-135231388;