chrX-136147468-A-C

Position:

• chrX-136147468-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000651929(FHL1):​c.-261A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.75 (17919 hom., 14859 hem., cov: 15)
  • Exomes 𝑓: 0.69 (87 hom. 93 hem.)
  • Failed GnomAD Quality Control
• Consequence: FHL1 ENST00000651929 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.643

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant X-136147468-A-C is Benign according to our data. Variant chrX-136147468-A-C is described in ClinVar as [Benign]. Clinvar id is 1248339.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.635 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FHL1	XM_047441926.1	c.-101+456A>C		intron_variant			XP_047297882.1
FHL1	NR_027621.2	n.311+456A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FHL1	ENST00000651929	c.-261A>C		5_prime_UTR_variant	1/7			ENSP00000499016.1
FHL1	ENST00000629039.2	c.-101+456A>C		intron_variant		2		ENSP00000486439.1

Frequencies

GnomAD3 genomes AF: 0.751 AC: 65343 AN: 86956 Hom.: 17917 Cov.: 15 AF XY: 0.810 AC XY: 14850 AN XY: 18344

Gnomad AFR AF: 0.617

Gnomad AMI AF: 0.768

Gnomad AMR AF: 0.750

Gnomad ASJ AF: 0.731

Gnomad EAS AF: 0.683

Gnomad SAS AF: 0.729

Gnomad FIN AF: 0.872

Gnomad MID AF: 0.695

Gnomad NFE AF: 0.817

Gnomad OTH AF: 0.711

GnomAD4 exome AF: 0.694 AC: 359 AN: 517 Hom.: 87 Cov.: 0 AF XY: 0.769 AC XY: 93 AN XY: 121

Gnomad4 SAS exome AF: 0.695

Gnomad4 NFE exome AF: 0.800

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.751 AC: 65347 AN: 86964 Hom.: 17919 Cov.: 15 AF XY: 0.809 AC XY: 14859 AN XY: 18362

Gnomad4 AFR AF: 0.617

Gnomad4 AMR AF: 0.750

Gnomad4 ASJ AF: 0.731

Gnomad4 EAS AF: 0.683

Gnomad4 SAS AF: 0.731

Gnomad4 FIN AF: 0.872

Gnomad4 NFE AF: 0.817

Gnomad4 OTH AF: 0.712

Alfa AF: 0.540 Hom.: 1680

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 23, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.7
DANN	Benign	0.73

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs28494155; hg19: chrX-135229627;