chr2-12994678-A-G

Variant names:

• chr2-12994678-A-G
• rs12692488
• ENST00000422996.2:n.950-2042T>C

Variant summary

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

The ENST00000422996.2(ENSG00000225649):​n.950-2042T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.46 in 151,986 control chromosomes in the GnomAD database, including 18,055 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 0.46 (18055 hom., cov: 31)
• Consequence: ENSG00000225649 ENST00000422996.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.857
• Publications: 2 publications found

Genes affected

ENSG00000225649 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.705 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000422996.2. 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
	LOC100506474	NR_038434.1		n.610+6910T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000225649	ENST00000422996.2	TSL:4	n.950-2042T>C		intron	N/A
	ENSG00000225649	ENST00000425974.5	TSL:2	n.610+6910T>C		intron	N/A
	ENSG00000225649	ENST00000653005.2		n.396+6910T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.460 AC: 69865 AN: 151866 Hom.: 18024 Cov.: 31

Gnomad AFR AF: 0.712

Gnomad AMI AF: 0.393

Gnomad AMR AF: 0.405

Gnomad ASJ AF: 0.386

Gnomad EAS AF: 0.481

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.399

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.350

Gnomad OTH AF: 0.425

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

GnomAD4 genome AF: 0.460 AC: 69956 AN: 151986 Hom.: 18055 Cov.: 31 AF XY: 0.456 AC XY: 33846 AN XY: 74296

African (AFR) AF: 0.712 AC: 29501 AN: 41460

American (AMR) AF: 0.405 AC: 6181 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.386 AC: 1339 AN: 3466

East Asian (EAS) AF: 0.481 AC: 2485 AN: 5162

South Asian (SAS) AF: 0.223 AC: 1076 AN: 4826

European-Finnish (FIN) AF: 0.399 AC: 4208 AN: 10556

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.350 AC: 23798 AN: 67946

Other (OTH) AF: 0.425 AC: 896 AN: 2110

Alfa AF: 0.384 Hom.: 38694

Bravo AF: 0.476

Asia WGS AF: 0.408 AC: 1417 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.30
DANN	Benign	0.67
PhyloP100		-0.86

Splicing

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

Other links and lift over

dbSNP: rs12692488; hg19: chr2-13134803;