12-40383514-T-G

Variant names:

• chr12-40383514-T-G
• rs12423567
• ENST00000724141.1:n.307+32787A>C

Variant summary

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

The ENST00000724141.1(ENSG00000258167):​n.307+32787A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 152,118 control chromosomes in the GnomAD database, including 6,342 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 0.28 (6342 hom., cov: 32)
• Consequence: ENSG00000258167 ENST00000724141.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.904
• Publications: 3 publications found

Genes affected

ENSG00000258167 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105369736	XR_944868.3	n.484+12398A>C		intron_variant	Intron 5 of 5
LOC105369736	XR_944869.3	n.485-11462A>C		intron_variant	Intron 5 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000258167	ENST00000724141.1	n.307+32787A>C		intron_variant	Intron 3 of 4
ENSG00000258167	ENST00000724142.1	n.170-34735A>C		intron_variant	Intron 2 of 3
ENSG00000258167	ENST00000724143.1	n.170-34735A>C		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42461 AN: 152000 Hom.: 6335 Cov.: 32

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.476

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.290

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

GnomAD4 genome AF: 0.279 AC: 42493 AN: 152118 Hom.: 6342 Cov.: 32 AF XY: 0.280 AC XY: 20826 AN XY: 74362

African (AFR) AF: 0.187 AC: 7760 AN: 41484

American (AMR) AF: 0.285 AC: 4360 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 994 AN: 3472

East Asian (EAS) AF: 0.134 AC: 693 AN: 5174

South Asian (SAS) AF: 0.260 AC: 1253 AN: 4824

European-Finnish (FIN) AF: 0.371 AC: 3927 AN: 10582

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.329 AC: 22379 AN: 67984

Other (OTH) AF: 0.286 AC: 603 AN: 2110

Alfa AF: 0.188 Hom.: 425

Bravo AF: 0.270

Asia WGS AF: 0.183 AC: 639 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.48
DANN	Benign	0.25
PhyloP100		-0.90

Splicing

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

Other links and lift over

dbSNP: rs12423567; hg19: chr12-40777316;