12-41916107-T-C

Variant names:

• chr12-41916107-T-C
• rs2215456
• ENST00000550874.1:n.471+16015A>G

Variant summary

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

The ENST00000550874.1(ENSG00000257239):​n.471+16015A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 152,000 control chromosomes in the GnomAD database, including 23,475 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 0.54 (23475 hom., cov: 32)
• Consequence: ENSG00000257239 ENST00000550874.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.211
• Publications: 6 publications found

Genes affected

ENSG00000257239 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.611 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
ENSG00000257239	ENST00000550874.1	n.471+16015A>G		intron_variant	Intron 1 of 1	3
ENSG00000257239	ENST00000824751.1	n.122+25422A>G		intron_variant	Intron 1 of 1
ENSG00000257239	ENST00000824752.1	n.243+25422A>G		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.545 AC: 82710 AN: 151882 Hom.: 23462 Cov.: 32

Gnomad AFR AF: 0.383

Gnomad AMI AF: 0.541

Gnomad AMR AF: 0.557

Gnomad ASJ AF: 0.587

Gnomad EAS AF: 0.595

Gnomad SAS AF: 0.601

Gnomad FIN AF: 0.638

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.616

Gnomad OTH AF: 0.558

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

GnomAD4 genome AF: 0.544 AC: 82755 AN: 152000 Hom.: 23475 Cov.: 32 AF XY: 0.545 AC XY: 40499 AN XY: 74294

African (AFR) AF: 0.382 AC: 15839 AN: 41450

American (AMR) AF: 0.557 AC: 8509 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.587 AC: 2038 AN: 3472

East Asian (EAS) AF: 0.594 AC: 3072 AN: 5172

South Asian (SAS) AF: 0.602 AC: 2897 AN: 4816

European-Finnish (FIN) AF: 0.638 AC: 6736 AN: 10552

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.616 AC: 41842 AN: 67958

Other (OTH) AF: 0.561 AC: 1185 AN: 2112

Alfa AF: 0.570 Hom.: 3984

Bravo AF: 0.529

Asia WGS AF: 0.589 AC: 2050 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.4
DANN	Benign	0.72
PhyloP100		0.21

Splicing

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

Other links and lift over

dbSNP: rs2215456; hg19: chr12-42309909; COSMIC: COSV73441619;