chr11-62981227-G-A

Variant names:

• chr11-62981227-G-A
• rs2276300
• NM_153276.3:c.921+33C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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]

ENSG00000301851 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153276.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A6	NM_153276.3	MANE Select	c.921+33C>T		intron	N/A	NP_695008.1
	SLC22A6	NM_004790.5		c.921+33C>T		intron	N/A	NP_004781.2
	SLC22A6	NM_153278.3		c.921+33C>T		intron	N/A	NP_695010.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A6	ENST00000360421.9	TSL:1 MANE Select	c.921+33C>T		intron	N/A	ENSP00000353597.4
	SLC22A6	ENST00000377871.7	TSL:1	c.921+33C>T		intron	N/A	ENSP00000367102.3
	SLC22A6	ENST00000421062.2	TSL:1	c.921+33C>T		intron	N/A	ENSP00000404441.2

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

GnomAD2 exomes AF: 0.0154 AC: 3700 AN: 239752 AF XY: 0.0148

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 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

African (AFR) AF: 0.000180 AC: 6 AN: 33410

American (AMR) AF: 0.00123 AC: 54 AN: 43896

Ashkenazi Jewish (ASJ) AF: 0.00227 AC: 59 AN: 25966

East Asian (EAS) AF: 0.153 AC: 6048 AN: 39492

South Asian (SAS) AF: 0.00774 AC: 659 AN: 85090

European-Finnish (FIN) AF: 0.00253 AC: 134 AN: 53066

Middle Eastern (MID) AF: 0.00156 AC: 9 AN: 5766

European-Non Finnish (NFE) AF: 0.000676 AC: 750 AN: 1109492

Other (OTH) AF: 0.00950 AC: 572 AN: 60202

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

African (AFR) AF: 0.000385 AC: 16 AN: 41588

American (AMR) AF: 0.00294 AC: 45 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00231 AC: 8 AN: 3470

East Asian (EAS) AF: 0.174 AC: 899 AN: 5172

South Asian (SAS) AF: 0.0126 AC: 61 AN: 4828

European-Finnish (FIN) AF: 0.00320 AC: 34 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00103 AC: 70 AN: 68040

Other (OTH) AF: 0.0109 AC: 23 AN: 2114

Alfa AF: 0.00205 Hom.: 17

Bravo AF: 0.00928

Asia WGS AF: 0.0670 AC: 232 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.8
DANN	Benign	0.62
PhyloP100		-0.78
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: rs2276300; hg19: chr11-62748699; COSMIC: COSV64559974;