chr12-6394334-G-C

Variant names:

• chr12-6394334-G-C
• rs12296430
• ENST00000541888.2:n.161+6G>C

Variant summary

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

The ENST00000541888.2(ENSG00000256433):​n.161+6G>C variant causes a splice region, intron 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: ENSG00000256433 ENST00000541888.2 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.107
• Publications: 28 publications found

Genes affected

ENSG00000256433 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000541888.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000256433	ENST00000541888.2	TSL:5	n.161+6G>C		splice_region intron	N/A
	ENSG00000256433	ENST00000663143.1		n.189+6G>C		splice_region intron	N/A

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

African (AFR) AF: 0.250 AC: 1 AN: 4

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.167 AC: 1 AN: 6

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.0714 AC: 1 AN: 14

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.225 AC: 23 AN: 102

Other (OTH) AF: 0.333 AC: 4 AN: 12

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

African (AFR) AF: 0.0785 AC: 3255 AN: 41482

American (AMR) AF: 0.309 AC: 4711 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 498 AN: 3468

East Asian (EAS) AF: 0.0415 AC: 215 AN: 5184

South Asian (SAS) AF: 0.127 AC: 610 AN: 4820

European-Finnish (FIN) AF: 0.207 AC: 2196 AN: 10588

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.194 AC: 13158 AN: 67966

Other (OTH) AF: 0.165 AC: 348 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.3
DANN	Benign	0.70
PhyloP100		-0.11

Splicing

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

Other links and lift over

dbSNP: rs12296430; hg19: chr12-6503500;