chrX-136180473-C-T

Variant names:

• chrX-136180473-C-T
• rs7061270
• NM_001159702.3:c.-27+10493C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001159702.3(FHL1):​c.-27+10493C>T 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 0.68 (18428 hom., 22543 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: FHL1 NM_001159702.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.105
• Publications: 2 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), Orphanet, G2P
• 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=-0.91).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FHL1	NM_001159702.3	c.-27+10493C>T		intron_variant	Intron 2 of 7	ENST00000394155.8	NP_001153174.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FHL1	ENST00000394155.8	c.-27+10493C>T		intron_variant	Intron 2 of 7	5	NM_001159702.3	ENSP00000377710.2

Frequencies

GnomAD3 genomes AF: 0.679 AC: 75154 AN: 110691 Hom.: 18426 Cov.: 23

Gnomad AFR AF: 0.499

Gnomad AMI AF: 0.737

Gnomad AMR AF: 0.676

Gnomad ASJ AF: 0.662

Gnomad EAS AF: 0.615

Gnomad SAS AF: 0.658

Gnomad FIN AF: 0.819

Gnomad MID AF: 0.645

Gnomad NFE AF: 0.774

Gnomad OTH AF: 0.644

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: 0.679 AC: 75181 AN: 110746 Hom.: 18428 Cov.: 23 AF XY: 0.683 AC XY: 22543 AN XY: 32992

African (AFR) AF: 0.499 AC: 15198 AN: 30469

American (AMR) AF: 0.677 AC: 7110 AN: 10507

Ashkenazi Jewish (ASJ) AF: 0.662 AC: 1734 AN: 2620

East Asian (EAS) AF: 0.615 AC: 2141 AN: 3484

South Asian (SAS) AF: 0.661 AC: 1722 AN: 2606

European-Finnish (FIN) AF: 0.819 AC: 4785 AN: 5839

Middle Eastern (MID) AF: 0.620 AC: 132 AN: 213

European-Non Finnish (NFE) AF: 0.774 AC: 40886 AN: 52814

Other (OTH) AF: 0.642 AC: 973 AN: 1516

Alfa AF: 0.725 Hom.: 8257

Bravo AF: 0.660

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.0
DANN	Benign	0.40
PhyloP100		-0.10
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs7061270; hg19: chrX-135262632;