rs12296430

chr12-6394334-G-C

Variant summary

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

The ENST00000541888.2(ENSG00000256433):n.161+6G>C variant causes a splice donor region, intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 152,232 control chromosomes in the GnomAD database, including 2,490 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 0.17 (2488 hom., cov: 32)
  • Exomes 𝑓: 0.22 (2 hom.)
• Consequence: ENST00000541888.2 splice_donor_region, intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.107

Genes affected

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000541888.2	n.161+6G>C		splice_donor_region_variant, intron_variant, non_coding_transcript_variant		5
	ENST00000663143.1	n.189+6G>C		splice_donor_region_variant, intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25156 AN: 151976 Hom.: 2481 Cov.: 32

Gnomad AFR AF: 0.0785

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.0418

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.167

GnomAD4 exome AF: 0.217 AC: 30 AN: 138 Hom.: 2 Cov.: 0 AF XY: 0.236 AC XY: 25 AN XY: 106

Gnomad4 AFR exome AF: 0.250

Gnomad4 EAS exome AF: 0.167

Gnomad4 FIN exome AF: 0.0714

Gnomad4 NFE exome AF: 0.225

Gnomad4 OTH exome AF: 0.333

GnomAD4 genome AF: 0.166 AC: 25184 AN: 152094 Hom.: 2488 Cov.: 32 AF XY: 0.167 AC XY: 12423 AN XY: 74354

Gnomad4 AFR AF: 0.0785

Gnomad4 AMR AF: 0.309

Gnomad4 ASJ AF: 0.144

Gnomad4 EAS AF: 0.0415

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.207

Gnomad4 NFE AF: 0.194

Gnomad4 OTH AF: 0.165

Alfa AF: 0.189 Hom.: 388

Bravo AF: 0.171

Asia WGS AF: 0.0760 AC: 266 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.3
Dann	Benign	0.70

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12296430; hg19: chr12-6503500;