rs2180062

Variant names:

• chrX-136149229-T-C
• rs2180062
• NM_001159702.3:c.-101+1601T>C

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Likely benign. The variant received -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
• Publications: 6 publications found

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]

FHL1 Gene-Disease associations (from GenCC):

• X-linked myopathy with postural muscle atrophy

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet
• myopathy, reducing body, X-linked, early-onset, severe

  Inheritance: XL Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• reducing body myopathy

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
• X-linked Emery-Dreifuss muscular dystrophy

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
• X-linked scapuloperoneal muscular dystrophy

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001159702.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FHL1	NM_001159702.3	MANE Plus Clinical	c.-101+1601T>C		intron	N/A	NP_001153174.1	Q13642-2
	FHL1	NM_001369326.1		c.-101+1351T>C		intron	N/A	NP_001356255.1	Q13642-2
	FHL1	NM_001369327.2		c.-101+1083T>C		intron	N/A	NP_001356256.1	Q13642-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FHL1	ENST00000394155.8	TSL:5 MANE Plus Clinical	c.-101+1601T>C		intron	N/A	ENSP00000377710.2	Q13642-2
	FHL1	ENST00000651089.1		c.-243+1351T>C		intron	N/A	ENSP00000498684.1	Q13642-2
	FHL1	ENST00000629039.2	TSL:2	c.-101+2217T>C		intron	N/A	ENSP00000486439.1	Q13642-1

Frequencies

GnomAD3 genomes AF: 0.641 AC: 71009 AN: 110859 Hom.: 17275 Cov.: 23

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

African (AFR) AF: 0.352 AC: 10756 AN: 30599

American (AMR) AF: 0.653 AC: 6818 AN: 10435

Ashkenazi Jewish (ASJ) AF: 0.679 AC: 1787 AN: 2630

East Asian (EAS) AF: 0.613 AC: 2151 AN: 3507

South Asian (SAS) AF: 0.661 AC: 1724 AN: 2608

European-Finnish (FIN) AF: 0.824 AC: 4821 AN: 5852

Middle Eastern (MID) AF: 0.635 AC: 134 AN: 211

European-Non Finnish (NFE) AF: 0.783 AC: 41403 AN: 52879

Other (OTH) AF: 0.611 AC: 929 AN: 1520

Alfa AF: 0.717 Hom.: 5887

Bravo AF: 0.615

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.54
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2180062; hg19: chrX-135231388;