11-63217225-T-C

Position:

• chr11-63217225-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_199352.6(SLC22A25):​c.830+89A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 1,444,334 control chromosomes in the GnomAD database, including 107,847 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 0.37 (10771 hom., cov: 33)
  • Exomes 𝑓: 0.38 (97076 hom.)
• Consequence: SLC22A25 NM_199352.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.169

Genes affected

SLC22A25 (HGNC:32935): (solute carrier family 22 member 25) Predicted to enable transmembrane transporter activity. Predicted to be involved in organic anion transport. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC22A25	NM_199352.6	c.830+89A>G		intron_variant		ENST00000306494.11	NP_955384.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC22A25	ENST00000306494.11	c.830+89A>G		intron_variant		1	NM_199352.6	ENSP00000307443.6
SLC22A25	ENST00000525295.1	n.402+12026A>G		intron_variant		1		ENSP00000435614.1
SLC22A25	ENST00000527057.5	n.824+89A>G		intron_variant		1		ENSP00000432242.1
SLC22A25	ENST00000528239.5	n.*479+89A>G		intron_variant		1		ENSP00000431235.1

Frequencies

GnomAD3 genomes AF: 0.372 AC: 56527 AN: 152010 Hom.: 10762 Cov.: 33

Gnomad AFR AF: 0.308

Gnomad AMI AF: 0.444

Gnomad AMR AF: 0.434

Gnomad ASJ AF: 0.538

Gnomad EAS AF: 0.563

Gnomad SAS AF: 0.516

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.367

Gnomad OTH AF: 0.393

GnomAD4 exome AF: 0.382 AC: 493991 AN: 1292206 Hom.: 97076 AF XY: 0.386 AC XY: 245596 AN XY: 636686

Gnomad4 AFR exome AF: 0.317

Gnomad4 AMR exome AF: 0.449

Gnomad4 ASJ exome AF: 0.546

Gnomad4 EAS exome AF: 0.587

Gnomad4 SAS exome AF: 0.509

Gnomad4 FIN exome AF: 0.321

Gnomad4 NFE exome AF: 0.364

Gnomad4 OTH exome AF: 0.394

GnomAD4 genome AF: 0.372 AC: 56577 AN: 152128 Hom.: 10771 Cov.: 33 AF XY: 0.377 AC XY: 28056 AN XY: 74388

Gnomad4 AFR AF: 0.308

Gnomad4 AMR AF: 0.434

Gnomad4 ASJ AF: 0.538

Gnomad4 EAS AF: 0.564

Gnomad4 SAS AF: 0.517

Gnomad4 FIN AF: 0.334

Gnomad4 NFE AF: 0.367

Gnomad4 OTH AF: 0.399

Alfa AF: 0.378 Hom.: 23046

Bravo AF: 0.375

Asia WGS AF: 0.503 AC: 1752 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	5.1
DANN	Benign	0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs7949840; hg19: chr11-62984697; COSMIC: COSV60594362;