X-136170075-AC-A

Position:

• chrX-136170075-AC-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001159702.3(FHL1):​c.-27+97delC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.749 in 196,933 control chromosomes in the GnomAD database, including 34,795 homozygotes. There are 55,407 hemizygotes in GnomAD. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.68 (18871 hom., 21327 hem., cov: 0)
  • Exomes 𝑓: 0.75 (34795 hom. 55407 hem.)
  • Failed GnomAD Quality Control
• Consequence: FHL1 NM_001159702.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.558

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 -10 ACMG points.

• BP6: Variant X-136170075-AC-A is Benign according to our data. Variant chrX-136170075-AC-A is described in ClinVar as [Benign]. Clinvar id is 1304791.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-136170075-AC-A is described in Lovd as [Likely_benign].
• BA1: GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.789 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FHL1	NM_001159702.3	c.-27+97delC		intron_variant		ENST00000394155.8	NP_001153174.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FHL1	ENST00000394155.8	c.-27+96delC		intron_variant		5	NM_001159702.3	ENSP00000377710.2

Frequencies

GnomAD3 genomes AF: 0.684 AC: 74498 AN: 108921 Hom.: 18870 Cov.: 0 AF XY: 0.681 AC XY: 21292 AN XY: 31245

Gnomad AFR AF: 0.498

Gnomad AMI AF: 0.735

Gnomad AMR AF: 0.675

Gnomad ASJ AF: 0.670

Gnomad EAS AF: 0.604

Gnomad SAS AF: 0.654

Gnomad FIN AF: 0.818

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.785

Gnomad OTH AF: 0.650

GnomAD4 exome AF: 0.749 AC: 147470 AN: 196933 Hom.: 34795 AF XY: 0.755 AC XY: 55407 AN XY: 73425

Gnomad4 AFR exome AF: 0.501

Gnomad4 AMR exome AF: 0.696

Gnomad4 ASJ exome AF: 0.695

Gnomad4 EAS exome AF: 0.615

Gnomad4 SAS exome AF: 0.701

Gnomad4 FIN exome AF: 0.828

Gnomad4 NFE exome AF: 0.794

Gnomad4 OTH exome AF: 0.729

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.684 AC: 74524 AN: 108975 Hom.: 18871 Cov.: 0 AF XY: 0.681 AC XY: 21327 AN XY: 31311

Gnomad4 AFR AF: 0.498

Gnomad4 AMR AF: 0.675

Gnomad4 ASJ AF: 0.670

Gnomad4 EAS AF: 0.604

Gnomad4 SAS AF: 0.657

Gnomad4 FIN AF: 0.818

Gnomad4 NFE AF: 0.785

Gnomad4 OTH AF: 0.647

Alfa AF: 0.743 Hom.: 6123

Bravo AF: 0.667

Asia WGS AF: 0.598 AC: 1510 AN: 2521

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 08, 2021

- -

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: rs3215593; hg19: chrX-135252234;