rs12557549

Variant names:

• chrX-67523723-C-T
• rs12557549

Variant summary

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

The variant allele was found at a frequency of 0.0121 in 110,785 control chromosomes in the GnomAD database, including 8 homozygotes. There are 375 hemizygotes in GnomAD. 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 (8 hom., 375 hem., cov: 22)
• Consequence: Unknown
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00
• Publications: 2 publications found

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0121 (1345/110785) while in subpopulation AMR AF = 0.02 (208/10388). AF 95% confidence interval is 0.0178. There are 8 homozygotes in GnomAd4. There are 375 alleles in the male GnomAd4 subpopulation. Median coverage is 22. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 8 gene

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

Frequencies

GnomAD3 genomes AF: 0.0122 AC: 1348 AN: 110733 Hom.: 8 Cov.: 22

Gnomad AFR AF: 0.00227

Gnomad AMI AF: 0.00730

Gnomad AMR AF: 0.0201

Gnomad ASJ AF: 0.0110

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00348

Gnomad FIN AF: 0.00202

Gnomad MID AF: 0.0417

Gnomad NFE AF: 0.0184

Gnomad OTH AF: 0.0208

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

GnomAD4 genome AF: 0.0121 AC: 1345 AN: 110785 Hom.: 8 Cov.: 22 AF XY: 0.0113 AC XY: 375 AN XY: 33097

African (AFR) AF: 0.00226 AC: 69 AN: 30474

American (AMR) AF: 0.0200 AC: 208 AN: 10388

Ashkenazi Jewish (ASJ) AF: 0.0110 AC: 29 AN: 2646

East Asian (EAS) AF: 0.00 AC: 0 AN: 3460

South Asian (SAS) AF: 0.00350 AC: 9 AN: 2574

European-Finnish (FIN) AF: 0.00202 AC: 12 AN: 5949

Middle Eastern (MID) AF: 0.0411 AC: 9 AN: 219

European-Non Finnish (NFE) AF: 0.0184 AC: 974 AN: 52883

Other (OTH) AF: 0.0199 AC: 30 AN: 1507

Alfa AF: 0.0150 Hom.: 97

Bravo AF: 0.0142

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.12
DANN	Benign	0.50
PhyloP100		-1.0

Splicing

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

Other links and lift over

dbSNP: rs12557549; hg19: chrX-66743565;