rs12459897

Variant names:

• chr19-31105872-G-T
• rs12459897
• ENST00000638312.1:n.191+5378G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000638312.1(ENSG00000284430):​n.191+5378G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0123 in 152,282 control chromosomes in the GnomAD database, including 23 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 0.012 (23 hom., cov: 32)
• Consequence: ENSG00000284430 ENST00000638312.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19
• Publications: 4 publications found

Genes affected

ENSG00000284430 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0123 (1868/152282) while in subpopulation NFE AF = 0.0179 (1220/68028). AF 95% confidence interval is 0.0171. There are 23 homozygotes in GnomAd4. There are 844 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 23 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC124900621	XR_935901.2	n.51+5378G>T		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000284430	ENST00000638312.1	n.191+5378G>T		intron_variant	Intron 1 of 5	5
ENSG00000284430	ENST00000718551.1	n.70+5378G>T		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes AF: 0.0123 AC: 1866 AN: 152164 Hom.: 23 Cov.: 32

Gnomad AFR AF: 0.00275

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.00864

Gnomad ASJ AF: 0.0268

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00332

Gnomad FIN AF: 0.0201

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0179

Gnomad OTH AF: 0.0105

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

GnomAD4 genome AF: 0.0123 AC: 1868 AN: 152282 Hom.: 23 Cov.: 32 AF XY: 0.0113 AC XY: 844 AN XY: 74462

African (AFR) AF: 0.00274 AC: 114 AN: 41554

American (AMR) AF: 0.00863 AC: 132 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0268 AC: 93 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5180

South Asian (SAS) AF: 0.00353 AC: 17 AN: 4820

European-Finnish (FIN) AF: 0.0201 AC: 213 AN: 10616

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0179 AC: 1220 AN: 68028

Other (OTH) AF: 0.0104 AC: 22 AN: 2114

Alfa AF: 0.0149 Hom.: 4

Bravo AF: 0.0119

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.30
DANN	Benign	0.40
PhyloP100		-1.2

Splicing

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

Other links and lift over

dbSNP: rs12459897; hg19: chr19-31596778;