6-135259815-T-C

Variant names:

• chr6-135259815-T-C
• rs2327587
• ENST00000434255.1:n.-181T>C

Variant summary

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

The ENST00000434255.1(ENSG00000224374):​n.-181T>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.637 in 152,128 control chromosomes in the GnomAD database, including 33,177 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 0.64 (33177 hom., cov: 33)
• Consequence: ENSG00000224374 ENST00000434255.1 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.987

Genes affected

ENSG00000224374 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.895 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000224374	ENST00000434255.1	n.-181T>C		upstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.636 AC: 96746 AN: 152010 Hom.: 33114 Cov.: 33

Gnomad AFR AF: 0.903

Gnomad AMI AF: 0.244

Gnomad AMR AF: 0.506

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.435

Gnomad SAS AF: 0.509

Gnomad FIN AF: 0.601

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.550

Gnomad OTH AF: 0.575

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

GnomAD4 genome AF: 0.637 AC: 96874 AN: 152128 Hom.: 33177 Cov.: 33 AF XY: 0.635 AC XY: 47185 AN XY: 74338

Gnomad4 AFR AF: 0.903

Gnomad4 AMR AF: 0.507

Gnomad4 ASJ AF: 0.465

Gnomad4 EAS AF: 0.434

Gnomad4 SAS AF: 0.509

Gnomad4 FIN AF: 0.601

Gnomad4 NFE AF: 0.550

Gnomad4 OTH AF: 0.580

Alfa AF: 0.560 Hom.: 17978

Bravo AF: 0.638

Asia WGS AF: 0.529 AC: 1837 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.37
DANN	Benign	0.42

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2327587; hg19: chr6-135580953;