rs2276300

Positions:

• chr11-62981227-G-A
• chr11-62981227-G-T

Variant summary

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

The NM_153276.3(SLC22A6):​c.921+33C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00587 in 1,608,726 control chromosomes in the GnomAD database, including 612 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 0.0076 (94 hom., cov: 32)
  • Exomes 𝑓: 0.0057 (518 hom.)
• Consequence: SLC22A6 NM_153276.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.782

Genes affected

SLC22A6 (HGNC:10970): (solute carrier family 22 member 6) The protein encoded by this gene is involved in the sodium-dependent transport and excretion of organic anions, some of which are potentially toxic. The encoded protein is an integral membrane protein and may be localized to the basolateral membrane. Four transcript variants encoding four different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC22A6	NM_153276.3	c.921+33C>T		intron_variant		ENST00000360421.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC22A6	ENST00000360421.9	c.921+33C>T		intron_variant		1	NM_153276.3	P1

Frequencies

GnomAD3 genomes AF: 0.00755 AC: 1149 AN: 152228 Hom.: 93 Cov.: 32

Gnomad AFR AF: 0.000386

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00294

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.0128

Gnomad FIN AF: 0.00320

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.00103

Gnomad OTH AF: 0.00717

GnomAD3 exomes AF: 0.0154 AC: 3700 AN: 239752 Hom.: 288 AF XY: 0.0148 AC XY: 1920 AN XY: 129456

Gnomad AFR exome AF: 0.000327

Gnomad AMR exome AF: 0.00129

Gnomad ASJ exome AF: 0.00204

Gnomad EAS exome AF: 0.179

Gnomad SAS exome AF: 0.00823

Gnomad FIN exome AF: 0.00232

Gnomad NFE exome AF: 0.00120

Gnomad OTH exome AF: 0.00930

GnomAD4 exome AF: 0.00569 AC: 8291 AN: 1456380 Hom.: 518 Cov.: 33 AF XY: 0.00578 AC XY: 4188 AN XY: 723942

Gnomad4 AFR exome AF: 0.000180

Gnomad4 AMR exome AF: 0.00123

Gnomad4 ASJ exome AF: 0.00227

Gnomad4 EAS exome AF: 0.153

Gnomad4 SAS exome AF: 0.00774

Gnomad4 FIN exome AF: 0.00253

Gnomad4 NFE exome AF: 0.000676

Gnomad4 OTH exome AF: 0.00950

GnomAD4 genome AF: 0.00759 AC: 1156 AN: 152346 Hom.: 94 Cov.: 32 AF XY: 0.00869 AC XY: 647 AN XY: 74496

Gnomad4 AFR AF: 0.000385

Gnomad4 AMR AF: 0.00294

Gnomad4 ASJ AF: 0.00231

Gnomad4 EAS AF: 0.174

Gnomad4 SAS AF: 0.0126

Gnomad4 FIN AF: 0.00320

Gnomad4 NFE AF: 0.00103

Gnomad4 OTH AF: 0.0109

Alfa AF: 0.00216 Hom.: 14

Bravo AF: 0.00928

Asia WGS AF: 0.0670 AC: 232 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.8
DANN	Benign	0.62

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: rs2276300; hg19: chr11-62748699; COSMIC: COSV64559974;