rs11568506

Positions:

• chr5-132335767-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000200652.4(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 ENST00000200652.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.104

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

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 27 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC22A4	NM_003059.3	c.1262-51G>A		intron_variant		ENST00000200652.4	NP_003050.2
MIR3936HG	NR_110997.1	n.561-841C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC22A4	ENST00000200652.4	c.1262-51G>A		intron_variant		1	NM_003059.3	ENSP00000200652	P1
MIR3936HG	ENST00000621103.4	n.561-841C>T		intron_variant, non_coding_transcript_variant		1
MIR3936HG	ENST00000616965.1	n.344-841C>T		intron_variant, non_coding_transcript_variant		5
MIR3936HG	ENST00000669845.1	n.187-841C>T		intron_variant, non_coding_transcript_variant

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

GnomAD3 exomes AF: 0.0171 AC: 4285 AN: 250286 Hom.: 54 AF XY: 0.0167 AC XY: 2256 AN XY: 135468

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 SAS exome AF: 0.00382

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

Gnomad4 AFR exome AF: 0.00294

Gnomad4 AMR exome AF: 0.0254

Gnomad4 ASJ exome AF: 0.00782

Gnomad4 EAS exome AF: 0.0000515

Gnomad4 SAS exome AF: 0.00358

Gnomad4 FIN exome AF: 0.0230

Gnomad4 NFE exome AF: 0.0231

Gnomad4 OTH exome AF: 0.0177

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

Gnomad4 AFR AF: 0.00366

Gnomad4 AMR AF: 0.0157

Gnomad4 ASJ AF: 0.0101

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00311

Gnomad4 FIN AF: 0.0242

Gnomad4 NFE AF: 0.0216

Gnomad4 OTH AF: 0.00992

Alfa AF: 0.0186 Hom.: 14

Bravo AF: 0.0142

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	10
DANN	Benign	0.74

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: rs11568506; hg19: chr5-131671460;