6-27478787-T-C

Variant names:

• chr6-27478787-T-C
• rs7749305
• ENST00000663193.1:n.265+3545T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000663193.1(ENSG00000286652):​n.265+3545T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0954 in 152,256 control chromosomes in the GnomAD database, including 833 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 0.095 (833 hom., cov: 33)
• Consequence: ENSG00000286652 ENST00000663193.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.35
• Publications: 31 publications found

Genes affected

ENSG00000286652 (HGNC:):

TRS-AGA2-2 (HGNC:34637):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRS-AGA2-2	unassigned_transcript_1013	c.-25T>C		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000286652	ENST00000663193.1	n.265+3545T>C		intron_variant	Intron 2 of 2
ENSG00000286652	ENST00000779964.1	n.279+3545T>C		intron_variant	Intron 2 of 3
ENSG00000286652	ENST00000779965.1	n.275+3545T>C		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.0954 AC: 14521 AN: 152138 Hom.: 834 Cov.: 33

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.0636

Gnomad ASJ AF: 0.0346

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.0388

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0978

Gnomad OTH AF: 0.0795

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

GnomAD4 genome AF: 0.0954 AC: 14524 AN: 152256 Hom.: 833 Cov.: 33 AF XY: 0.0883 AC XY: 6576 AN XY: 74444

African (AFR) AF: 0.146 AC: 6057 AN: 41528

American (AMR) AF: 0.0635 AC: 972 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0346 AC: 120 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5184

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4826

European-Finnish (FIN) AF: 0.0388 AC: 412 AN: 10612

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0977 AC: 6647 AN: 68022

Other (OTH) AF: 0.0796 AC: 168 AN: 2110

Alfa AF: 0.0976 Hom.: 1597

Bravo AF: 0.100

Asia WGS AF: 0.0130 AC: 46 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	0.28
DANN	Benign	0.33
PhyloP100		-3.4

Splicing

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

Other links and lift over

dbSNP: rs7749305; hg19: chr6-27446566;