15-48646849-T-C

Variant names:

• chr15-48646849-T-C
• rs6493333
• ENST00000752571.1:n.750T>C

Variant summary

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

The NR_183871.1(FBN1-DT):​n.1045T>C 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 0.837 in 152,152 control chromosomes in the GnomAD database, including 53,332 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 0.84 (53324 hom., cov: 31)
  • Exomes 𝑓: 0.94 (8 hom.)
• Consequence: FBN1-DT NR_183871.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.404
• Publications: 10 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.84 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NR_183871.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBN1-DT	NR_183871.1		n.1045T>C		non_coding_transcript_exon	Exon 1 of 2
	FBN1-DT	NR_183872.1		n.1026+19T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBN1-DT	ENST00000752571.1		n.750T>C		non_coding_transcript_exon	Exon 1 of 2
	FBN1-DT	ENST00000558061.2	TSL:3	n.925+19T>C		intron	N/A
	FBN1-DT	ENST00000752572.1		n.904+19T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.837 AC: 127264 AN: 152016 Hom.: 53275 Cov.: 31

Gnomad AFR AF: 0.816

Gnomad AMI AF: 0.814

Gnomad AMR AF: 0.839

Gnomad ASJ AF: 0.814

Gnomad EAS AF: 0.853

Gnomad SAS AF: 0.835

Gnomad FIN AF: 0.871

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.845

Gnomad OTH AF: 0.821

GnomAD4 exome AF: 0.944 AC: 17 AN: 18 Hom.: 8 Cov.: 0 AF XY: 1.00 AC XY: 10 AN XY: 10

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 2 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 1.00 AC: 4 AN: 4

Middle Eastern (MID) AF: 1.00 AC: 2 AN: 2

European-Non Finnish (NFE) AF: 0.833 AC: 5 AN: 6

Other (OTH) AF: 1.00 AC: 4 AN: 4

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.837 AC: 127364 AN: 152134 Hom.: 53324 Cov.: 31 AF XY: 0.839 AC XY: 62377 AN XY: 74372

African (AFR) AF: 0.816 AC: 33865 AN: 41482

American (AMR) AF: 0.839 AC: 12816 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.814 AC: 2827 AN: 3472

East Asian (EAS) AF: 0.854 AC: 4398 AN: 5152

South Asian (SAS) AF: 0.838 AC: 4039 AN: 4822

European-Finnish (FIN) AF: 0.871 AC: 9246 AN: 10610

Middle Eastern (MID) AF: 0.782 AC: 230 AN: 294

European-Non Finnish (NFE) AF: 0.845 AC: 57484 AN: 68000

Other (OTH) AF: 0.813 AC: 1718 AN: 2112

Alfa AF: 0.840 Hom.: 216217

Bravo AF: 0.836

Asia WGS AF: 0.799 AC: 2778 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.3
DANN	Benign	0.71
PhyloP100		-0.40

Splicing

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

Other links and lift over

dbSNP: rs6493333; hg19: chr15-48939046;