X-112403236-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001395362.2(RTL4):c.-284-27878C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.63 (16608 hom., 20673 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: RTL4 NM_001395362.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.343

Genes affected

RTL4 (HGNC:25214): (retrotransposon Gag like 4) Predicted to enable nucleic acid binding activity and zinc ion binding activity. Predicted to act upstream of or within cognition and norepinephrine metabolic process. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BS2: High Homozygotes in GnomAd at 16618 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RTL4	NM_001395362.2	c.-284-27878C>T		intron_variant		ENST00000695839.1
RTL4	NM_001004308.3	c.-229-51264C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RTL4	ENST00000695839.1	c.-284-27878C>T		intron_variant			NM_001395362.2	P1
RTL4	ENST00000340433.4	c.-284-27878C>T		intron_variant				P1
RTL4	ENST00000695808.1	c.-229-51264C>T		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.633 AC: 69901 AN: 110386 Hom.: 16618 Cov.: 22 AF XY: 0.633 AC XY: 20655 AN XY: 32646

Gnomad AFR AF: 0.390

Gnomad AMI AF: 0.822

Gnomad AMR AF: 0.680

Gnomad ASJ AF: 0.798

Gnomad EAS AF: 0.640

Gnomad SAS AF: 0.628

Gnomad FIN AF: 0.714

Gnomad MID AF: 0.675

Gnomad NFE AF: 0.744

Gnomad OTH AF: 0.660

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.633 AC: 69891 AN: 110437 Hom.: 16608 Cov.: 22 AF XY: 0.632 AC XY: 20673 AN XY: 32705

Gnomad4 AFR AF: 0.389

Gnomad4 AMR AF: 0.680

Gnomad4 ASJ AF: 0.798

Gnomad4 EAS AF: 0.640

Gnomad4 SAS AF: 0.629

Gnomad4 FIN AF: 0.714

Gnomad4 NFE AF: 0.744

Gnomad4 OTH AF: 0.654

Alfa AF: 0.727 Hom.: 56625

Bravo AF: 0.623

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	3.8
Dann	Benign	0.80

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs5982533; hg19: chrX-111646464;