X-136169520-G-GA

Position:

• chrX-136169520-G-GA

Variant summary

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

The NM_001159704.1(FHL1):​c.-478dupA variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.68 (18535 hom., 18546 hem., cov: 0)
  • Exomes 𝑓: 0.65 (13909 hom. 15785 hem.)
  • Failed GnomAD Quality Control
• Consequence: FHL1 NM_001159704.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0940

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant X-136169520-G-GA is Benign according to our data. Variant chrX-136169520-G-GA is described in ClinVar as [Benign]. Clinvar id is 1249824.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.691 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FHL1	NM_001159702.3	c.-100-378dupA		intron_variant		ENST00000394155.8	NP_001153174.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FHL1	ENST00000394155.8	c.-100-378dupA		intron_variant		5	NM_001159702.3	ENSP00000377710.2

Frequencies

GnomAD3 genomes AF: 0.676 AC: 71059 AN: 105060 Hom.: 18535 Cov.: 0 AF XY: 0.661 AC XY: 18531 AN XY: 28042

Gnomad AFR AF: 0.491

Gnomad AMI AF: 0.733

Gnomad AMR AF: 0.665

Gnomad ASJ AF: 0.657

Gnomad EAS AF: 0.601

Gnomad SAS AF: 0.637

Gnomad FIN AF: 0.794

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.781

Gnomad OTH AF: 0.640

GnomAD4 exome AF: 0.653 AC: 59462 AN: 91100 Hom.: 13909 Cov.: 0 AF XY: 0.615 AC XY: 15785 AN XY: 25686

Gnomad4 AFR exome AF: 0.404

Gnomad4 AMR exome AF: 0.596

Gnomad4 ASJ exome AF: 0.586

Gnomad4 EAS exome AF: 0.519

Gnomad4 SAS exome AF: 0.573

Gnomad4 FIN exome AF: 0.736

Gnomad4 NFE exome AF: 0.697

Gnomad4 OTH exome AF: 0.643

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.676 AC: 71066 AN: 105096 Hom.: 18535 Cov.: 0 AF XY: 0.660 AC XY: 18546 AN XY: 28086

Gnomad4 AFR AF: 0.491

Gnomad4 AMR AF: 0.666

Gnomad4 ASJ AF: 0.657

Gnomad4 EAS AF: 0.600

Gnomad4 SAS AF: 0.639

Gnomad4 FIN AF: 0.794

Gnomad4 NFE AF: 0.781

Gnomad4 OTH AF: 0.637

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

Apr 08, 2019

- -

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: rs397710404; hg19: chrX-135251679;