rs6837311

Positions:

• chr4-99274116-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000509295.5(ENSG00000246090):​n.695-9T>A variant causes a splice polypyrimidine tract, intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 152,208 control chromosomes in the GnomAD database, including 7,056 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 0.27 (7056 hom., cov: 33)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: ENST00000509295.5 splice_polypyrimidine_tract, intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0950

Genes affected

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC100507053	NR_037884.1	n.3790-12679T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000500358.6	n.3790-12679T>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41770 AN: 152088 Hom.: 7060 Cov.: 33

Gnomad AFR AF: 0.100

Gnomad AMI AF: 0.470

Gnomad AMR AF: 0.263

Gnomad ASJ AF: 0.462

Gnomad EAS AF: 0.0261

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.369

Gnomad NFE AF: 0.386

Gnomad OTH AF: 0.330

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.274 AC: 41773 AN: 152206 Hom.: 7056 Cov.: 33 AF XY: 0.268 AC XY: 19921 AN XY: 74410

Gnomad4 AFR AF: 0.100

Gnomad4 AMR AF: 0.263

Gnomad4 ASJ AF: 0.462

Gnomad4 EAS AF: 0.0262

Gnomad4 SAS AF: 0.157

Gnomad4 FIN AF: 0.345

Gnomad4 NFE AF: 0.386

Gnomad4 OTH AF: 0.327

Alfa AF: 0.328 Hom.: 1117

Bravo AF: 0.260

Asia WGS AF: 0.0990 AC: 348 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.9
DANN	Benign	0.44

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6837311; hg19: chr4-100195273;