11-64556035-C-T

Variant names:

• chr11-64556035-C-T
• rs72559736
• NM_018484.4:c.36C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_018484.4(SLC22A11):​c.36C>T​(p.Gly12Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00115 in 1,612,884 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0061 (12 hom., cov: 32)
  • Exomes 𝑓: 0.00064 (10 hom.)
• Consequence: SLC22A11 NM_018484.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.84
• Publications: 2 publications found

Genes affected

SLC22A11 (HGNC:18120): (solute carrier family 22 member 11) The protein encoded by this gene is involved in the sodium-independent transport and excretion of organic anions, some of which are potentially toxic. The encoded protein is an integral membrane protein and is found mainly in the kidney and in the placenta, where it may act to prevent potentially harmful organic anions from reaching the fetus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 11-64556035-C-T is Benign according to our data. Variant chr11-64556035-C-T is described in ClinVar as Benign. ClinVar VariationId is 711553.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.84 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00613 (934/152324) while in subpopulation AFR AF = 0.0206 (856/41562). AF 95% confidence interval is 0.0195. There are 12 homozygotes in GnomAd4. There are 422 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 12 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018484.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A11	NM_018484.4	MANE Select	c.36C>T	p.Gly12Gly	synonymous	Exon 1 of 10	NP_060954.1	Q9NSA0-1
	SLC22A11	NM_001307985.2		c.36C>T	p.Gly12Gly	synonymous	Exon 1 of 8	NP_001294914.1	Q9NSA0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A11	ENST00000301891.9	TSL:1 MANE Select	c.36C>T	p.Gly12Gly	synonymous	Exon 1 of 10	ENSP00000301891.4	Q9NSA0-1
	SLC22A11	ENST00000377581.7	TSL:5	c.36C>T	p.Gly12Gly	synonymous	Exon 1 of 9	ENSP00000366804.3	A6NCG2
	SLC22A11	ENST00000377585.7	TSL:2	c.36C>T	p.Gly12Gly	synonymous	Exon 1 of 8	ENSP00000366809.3	Q9NSA0-2

Frequencies

GnomAD3 genomes AF: 0.00614 AC: 934 AN: 152206 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.0206

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00392

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00334

GnomAD2 exomes AF: 0.00161 AC: 403 AN: 250094 AF XY: 0.00118

Gnomad AFR exome AF: 0.0207

Gnomad AMR exome AF: 0.00145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000882

Gnomad OTH exome AF: 0.000819

GnomAD4 exome AF: 0.000635 AC: 928 AN: 1460560 Hom.: 10 Cov.: 31 AF XY: 0.000564 AC XY: 410 AN XY: 726626

African (AFR) AF: 0.0217 AC: 725 AN: 33478

American (AMR) AF: 0.00139 AC: 62 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52230

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5766

European-Non Finnish (NFE) AF: 0.0000477 AC: 53 AN: 1111936

Other (OTH) AF: 0.00134 AC: 81 AN: 60376

GnomAD4 genome AF: 0.00613 AC: 934 AN: 152324 Hom.: 12 Cov.: 32 AF XY: 0.00567 AC XY: 422 AN XY: 74480

African (AFR) AF: 0.0206 AC: 856 AN: 41562

American (AMR) AF: 0.00392 AC: 60 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68026

Other (OTH) AF: 0.00331 AC: 7 AN: 2116

Alfa AF: 0.00254 Hom.: 4

Bravo AF: 0.00697

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	1.2
DANN	Benign	0.48
PhyloP100		-1.8
PromoterAI		0.026	Neutral
Mutation Taster		=100/0	polymorphism

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: rs72559736; hg19: chr11-64323507;