rs141159367

Variant names:

• chr11-64556004-C-T
• rs141159367
• NM_018484.4:c.5C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-64556004-C-T
• chr11-64556004-C-A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_018484.4(SLC22A11):​c.5C>T​(p.Ala2Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00282 in 1,605,046 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0019 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0029 (14 hom.)
• Consequence: SLC22A11 NM_018484.4 missense
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.0330
• Publications: 13 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.01748842).
• BP6: Variant 11-64556004-C-T is Benign according to our data. Variant chr11-64556004-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3042024.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAdExome4 at 14 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.5C>T	p.Ala2Val	missense	Exon 1 of 10	NP_060954.1	Q9NSA0-1
	SLC22A11	NM_001307985.2		c.5C>T	p.Ala2Val	missense	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.5C>T	p.Ala2Val	missense	Exon 1 of 10	ENSP00000301891.4	Q9NSA0-1
	SLC22A11	ENST00000377581.7	TSL:5	c.5C>T	p.Ala2Val	missense	Exon 1 of 9	ENSP00000366804.3	A6NCG2
	SLC22A11	ENST00000377585.7	TSL:2	c.5C>T	p.Ala2Val	missense	Exon 1 of 8	ENSP00000366809.3	Q9NSA0-2

Frequencies

GnomAD3 genomes AF: 0.00189 AC: 287 AN: 152200 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000627

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00452

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00310

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.00154 AC: 377 AN: 244776 AF XY: 0.00156

Gnomad AFR exome AF: 0.000801

Gnomad AMR exome AF: 0.000320

Gnomad ASJ exome AF: 0.000102

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00317

Gnomad NFE exome AF: 0.00258

Gnomad OTH exome AF: 0.000997

GnomAD4 exome AF: 0.00291 AC: 4232 AN: 1452728 Hom.: 14 Cov.: 31 AF XY: 0.00282 AC XY: 2035 AN XY: 722556

African (AFR) AF: 0.000539 AC: 18 AN: 33386

American (AMR) AF: 0.000247 AC: 11 AN: 44478

Ashkenazi Jewish (ASJ) AF: 0.0000774 AC: 2 AN: 25826

East Asian (EAS) AF: 0.00 AC: 0 AN: 39626

South Asian (SAS) AF: 0.0000233 AC: 2 AN: 85914

European-Finnish (FIN) AF: 0.00388 AC: 186 AN: 47960

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.00352 AC: 3908 AN: 1109588

Other (OTH) AF: 0.00174 AC: 105 AN: 60194

GnomAD4 genome AF: 0.00188 AC: 287 AN: 152318 Hom.: 0 Cov.: 32 AF XY: 0.00172 AC XY: 128 AN XY: 74474

African (AFR) AF: 0.000625 AC: 26 AN: 41574

American (AMR) AF: 0.0000654 AC: 1 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00452 AC: 48 AN: 10620

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

European-Non Finnish (NFE) AF: 0.00310 AC: 211 AN: 68026

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.00226 Hom.: 2

Bravo AF: 0.00156

TwinsUK AF: 0.00216 AC: 8

ALSPAC AF: 0.00337 AC: 13

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00361 AC: 31

ExAC AF: 0.00148 AC: 180

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00262

EpiControl AF: 0.00196

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	SLC22A11-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	15
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.087
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.074	D
MetaRNN	Benign	0.017	T
MetaSVM	Benign	-0.55	T
MutationAssessor	Pathogenic	3.2	M
PhyloP100		-0.033
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.17
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.094
MVP		0.81
MPC		0.49
ClinPred		0.059	T
GERP RS		1.7
PromoterAI		-0.095	Neutral
Varity_R		0.31
gMVP		0.19
Mutation Taster		=99/1	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: rs141159367; hg19: chr11-64323476; COSMIC: COSV104622853;