X-136147571-C-T

Position:

• chrX-136147571-C-T

Variant summary

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

The NM_001159702.3(FHL1):​c.-158C>T 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 0.028 (100 hom., 738 hem., cov: 20)
  • Exomes 𝑓: 0.0012 (0 hom. 0 hem.)
• Consequence: FHL1 NM_001159702.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.233

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant X-136147571-C-T is Benign according to our data. Variant chrX-136147571-C-T is described in ClinVar as [Benign]. Clinvar id is 1281259.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0915 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FHL1	NM_001159702.3	c.-158C>T		5_prime_UTR_variant	1/8	ENST00000394155.8	NP_001153174.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FHL1	ENST00000394155.8	c.-158C>T		5_prime_UTR_variant	1/8	5	NM_001159702.3	ENSP00000377710

Frequencies

GnomAD3 genomes AF: 0.0277 AC: 2987 AN: 107993 Hom.: 99 Cov.: 20 AF XY: 0.0236 AC XY: 737 AN XY: 31181

Gnomad AFR AF: 0.0944

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00947

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000787

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000466

Gnomad OTH AF: 0.0276

GnomAD4 exome AF: 0.00123 AC: 2 AN: 1624 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 690

Gnomad4 AFR exome AF: 0.118

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0277 AC: 2992 AN: 108034 Hom.: 100 Cov.: 20 AF XY: 0.0236 AC XY: 738 AN XY: 31232

Gnomad4 AFR AF: 0.0944

Gnomad4 AMR AF: 0.00956

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000790

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000466

Gnomad4 OTH AF: 0.0272

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 25, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	13
DANN	Uncertain	0.98

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs777858178; hg19: chrX-135229730; COSMIC: COSV65781112; COSMIC: COSV65781112;