NM_003059.3:c.1262-51G>A

Variant names:

• chr5-132335767-G-A
• rs11568506
• NM_003059.3:c.1262-51G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_003059.3(SLC22A4):​c.1262-51G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0196 in 1,439,874 control chromosomes in the GnomAD database, including 354 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 0.014 (27 hom., cov: 32)
  • Exomes 𝑓: 0.020 (327 hom.)
• Consequence: SLC22A4 NM_003059.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.104
• Publications: 7 publications found

Genes affected

SLC22A4 (HGNC:10968): (solute carrier family 22 member 4) Polyspecific organic cation transporters in the liver, kidney, intestine, and other organs are critical for elimination of many endogenous small organic cations as well as a wide array of drugs and environmental toxins. The encoded protein is an organic cation transporter and plasma integral membrane protein containing eleven putative transmembrane domains as well as a nucleotide-binding site motif. Transport by this protein is at least partially ATP-dependent. [provided by RefSeq, Jul 2008]

MIR3936HG (HGNC:40538): (MIR3936 host gene)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0145 (2204/152314) while in subpopulation NFE AF = 0.0216 (1472/68024). AF 95% confidence interval is 0.0207. There are 27 homozygotes in GnomAd4. There are 1043 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 27 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003059.3. 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
	SLC22A4	NM_003059.3	MANE Select	c.1262-51G>A		intron	N/A	NP_003050.2
	MIR3936HG	NR_110997.1		n.561-841C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A4	ENST00000200652.4	TSL:1 MANE Select	c.1262-51G>A		intron	N/A	ENSP00000200652.3
	MIR3936HG	ENST00000621103.4	TSL:1	n.561-841C>T		intron	N/A
	MIR3936HG	ENST00000616965.1	TSL:5	n.344-841C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0145 AC: 2204 AN: 152196 Hom.: 27 Cov.: 32

Gnomad AFR AF: 0.00364

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0158

Gnomad ASJ AF: 0.0101

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00311

Gnomad FIN AF: 0.0242

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0216

Gnomad OTH AF: 0.0100

GnomAD2 exomes AF: 0.0171 AC: 4285 AN: 250286 AF XY: 0.0167

Gnomad AFR exome AF: 0.00334

Gnomad AMR exome AF: 0.0258

Gnomad ASJ exome AF: 0.00854

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.0229

Gnomad NFE exome AF: 0.0222

Gnomad OTH exome AF: 0.0216

GnomAD4 exome AF: 0.0202 AC: 25961 AN: 1287560 Hom.: 327 Cov.: 19 AF XY: 0.0195 AC XY: 12674 AN XY: 650212

African (AFR) AF: 0.00294 AC: 88 AN: 29972

American (AMR) AF: 0.0254 AC: 1129 AN: 44476

Ashkenazi Jewish (ASJ) AF: 0.00782 AC: 196 AN: 25074

East Asian (EAS) AF: 0.0000515 AC: 2 AN: 38866

South Asian (SAS) AF: 0.00358 AC: 295 AN: 82498

European-Finnish (FIN) AF: 0.0230 AC: 1212 AN: 52798

Middle Eastern (MID) AF: 0.00429 AC: 22 AN: 5132

European-Non Finnish (NFE) AF: 0.0231 AC: 22049 AN: 954116

Other (OTH) AF: 0.0177 AC: 968 AN: 54628

GnomAD4 genome AF: 0.0145 AC: 2204 AN: 152314 Hom.: 27 Cov.: 32 AF XY: 0.0140 AC XY: 1043 AN XY: 74470

African (AFR) AF: 0.00366 AC: 152 AN: 41568

American (AMR) AF: 0.0157 AC: 240 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0101 AC: 35 AN: 3472

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

South Asian (SAS) AF: 0.00311 AC: 15 AN: 4826

European-Finnish (FIN) AF: 0.0242 AC: 257 AN: 10610

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

European-Non Finnish (NFE) AF: 0.0216 AC: 1472 AN: 68024

Other (OTH) AF: 0.00992 AC: 21 AN: 2116

Alfa AF: 0.0189 Hom.: 23

Bravo AF: 0.0142

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	10
DANN	Benign	0.74
PhyloP100		-0.10
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: rs11568506; hg19: chr5-131671460;