11-63217225-T-C

Variant names:

• chr11-63217225-T-C
• rs7949840
• NM_199352.6:c.830+89A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SLC22A25	NM_199352.6	c.830+89A>G		intron_variant	Intron 7 of 11	ENST00000306494.11	NP_955384.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A25	ENST00000306494.11	c.830+89A>G		intron_variant	Intron 7 of 11	1	NM_199352.6	ENSP00000307443.6
SLC22A25	ENST00000525295.1	n.402+12026A>G		intron_variant	Intron 1 of 6	1		ENSP00000435614.1
SLC22A25	ENST00000527057.5	n.824+89A>G		intron_variant	Intron 4 of 9	1		ENSP00000432242.1
SLC22A25	ENST00000528239.5	n.*479+89A>G		intron_variant	Intron 6 of 10	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

African (AFR) AF: 0.317 AC: 9520 AN: 29986

American (AMR) AF: 0.449 AC: 14875 AN: 33162

Ashkenazi Jewish (ASJ) AF: 0.546 AC: 11396 AN: 20874

East Asian (EAS) AF: 0.587 AC: 22244 AN: 37902

South Asian (SAS) AF: 0.509 AC: 35265 AN: 69262

European-Finnish (FIN) AF: 0.321 AC: 13184 AN: 41126

Middle Eastern (MID) AF: 0.465 AC: 2446 AN: 5260

European-Non Finnish (NFE) AF: 0.364 AC: 363596 AN: 1000210

Other (OTH) AF: 0.394 AC: 21465 AN: 54424

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

African (AFR) AF: 0.308 AC: 12776 AN: 41480

American (AMR) AF: 0.434 AC: 6623 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.538 AC: 1868 AN: 3472

East Asian (EAS) AF: 0.564 AC: 2915 AN: 5172

South Asian (SAS) AF: 0.517 AC: 2497 AN: 4830

European-Finnish (FIN) AF: 0.334 AC: 3541 AN: 10588

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.367 AC: 24972 AN: 68004

Other (OTH) AF: 0.399 AC: 842 AN: 2110

Alfa AF: 0.374 Hom.: 34272

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
PhyloP100		-0.17
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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