15-48646984-A-T

Variant names:

• chr15-48646984-A-T
• rs6493334
• ENST00000752571.1:n.885A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000752571.1(FBN1-DT):​n.885A>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 152,140 control chromosomes in the GnomAD database, including 8,314 homozygotes. 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 0.28 (8314 hom., cov: 32)
• Consequence: FBN1-DT ENST00000752571.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.10
• Publications: 7 publications found

Genes affected

FBN1-DT (HGNC:55413): (FBN1 divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.544 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000752571.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBN1-DT	NR_183871.1		n.1180A>T		non_coding_transcript_exon	Exon 1 of 2
	FBN1-DT	NR_183872.1		n.1026+154A>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBN1-DT	ENST00000752571.1		n.885A>T		non_coding_transcript_exon	Exon 1 of 2
	FBN1-DT	ENST00000558061.2	TSL:3	n.925+154A>T		intron	N/A
	FBN1-DT	ENST00000752572.1		n.904+154A>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.277 AC: 42071 AN: 152022 Hom.: 8299 Cov.: 32

Gnomad AFR AF: 0.551

Gnomad AMI AF: 0.304

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.0640

Gnomad EAS AF: 0.412

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.225

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

GnomAD4 genome AF: 0.277 AC: 42126 AN: 152140 Hom.: 8314 Cov.: 32 AF XY: 0.276 AC XY: 20513 AN XY: 74386

African (AFR) AF: 0.550 AC: 22813 AN: 41452

American (AMR) AF: 0.188 AC: 2868 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0640 AC: 222 AN: 3470

East Asian (EAS) AF: 0.412 AC: 2133 AN: 5172

South Asian (SAS) AF: 0.202 AC: 973 AN: 4828

European-Finnish (FIN) AF: 0.205 AC: 2174 AN: 10600

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.149 AC: 10167 AN: 68012

Other (OTH) AF: 0.222 AC: 469 AN: 2108

Alfa AF: 0.0958 Hom.: 149

Bravo AF: 0.290

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.2
DANN	Benign	0.57
PhyloP100		1.1

Splicing

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

Other links and lift over

dbSNP: rs6493334; hg19: chr15-48939181;