X-136147722-C-G

Position:

• chrX-136147722-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001159702.3(FHL1):​c.-101+94C>G variant causes a intron 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.014 (16 hom., 394 hem., cov: 19)
  • Exomes 𝑓: 0.0016 (0 hom. 0 hem.)
• Consequence: FHL1 NM_001159702.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.08

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant X-136147722-C-G is Benign according to our data. Variant chrX-136147722-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 1212687.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0142 (1528/107918) while in subpopulation AFR AF= 0.0207 (618/29785). AF 95% confidence interval is 0.0194. There are 16 homozygotes in gnomad4. There are 394 alleles in male gnomad4 subpopulation. Median coverage is 19. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 16 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FHL1	NM_001159702.3	c.-101+94C>G		intron_variant		ENST00000394155.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FHL1	ENST00000394155.8	c.-101+94C>G		intron_variant		5	NM_001159702.3

Frequencies

GnomAD3 genomes AF: 0.0142 AC: 1527 AN: 107884 Hom.: 16 Cov.: 19 AF XY: 0.0128 AC XY: 394 AN XY: 30816

Gnomad AFR AF: 0.0208

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.00858

Gnomad ASJ AF: 0.0474

Gnomad EAS AF: 0.00752

Gnomad SAS AF: 0.00203

Gnomad FIN AF: 0.00509

Gnomad MID AF: 0.0174

Gnomad NFE AF: 0.0103

Gnomad OTH AF: 0.0139

GnomAD4 exome AF: 0.00164 AC: 1 AN: 608 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 186

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00247

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0142 AC: 1528 AN: 107918 Hom.: 16 Cov.: 19 AF XY: 0.0128 AC XY: 394 AN XY: 30860

Gnomad4 AFR AF: 0.0207

Gnomad4 AMR AF: 0.00857

Gnomad4 ASJ AF: 0.0474

Gnomad4 EAS AF: 0.00756

Gnomad4 SAS AF: 0.00245

Gnomad4 FIN AF: 0.00509

Gnomad4 NFE AF: 0.0103

Gnomad4 OTH AF: 0.0137

Bravo AF: 0.0149

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 21, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.2
DANN	Benign	0.50

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs374235006; hg19: chrX-135229881;