chr11-63144186-T-C

Variant names:

• chr11-63144186-T-C
• rs1939747
• NM_001136506.2:c.-407A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001136506.2(SLC22A24):​c.-407A>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.763 in 157,238 control chromosomes in the GnomAD database, including 47,338 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 0.76 (45553 hom., cov: 31)
  • Exomes 𝑓: 0.83 (1785 hom.)
• Consequence: SLC22A24 NM_001136506.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.458
• Publications: 7 publications found

Genes affected

SLC22A24 (HGNC:28542): (solute carrier family 22 member 24) SLC22A24 belongs to a large family of transmembrane proteins that function as uniporters, symporters, and antiporters to transport organic ions across cell membranes (Jacobsson et al., 2007 [PubMed 17714910]).[supplied by OMIM, Mar 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.88 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A24	NM_001136506.2	c.-407A>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 10	ENST00000612278.4	NP_001129978.2
SLC22A24	NM_001136506.2	c.-407A>G		5_prime_UTR_variant	Exon 1 of 10	ENST00000612278.4	NP_001129978.2
SLC22A24	NM_173586.3	c.-407A>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 4		NP_775857.2
SLC22A24	NM_173586.3	c.-407A>G		5_prime_UTR_variant	Exon 1 of 4		NP_775857.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A24	ENST00000612278.4	c.-407A>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 10	5	NM_001136506.2	ENSP00000480336.1
SLC22A24	ENST00000417740.5	c.-407A>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 10	5		ENSP00000396586.1
SLC22A24	ENST00000326192.5	c.-407A>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 4	1		ENSP00000321549.5
SLC22A24	ENST00000612278.4	c.-407A>G		5_prime_UTR_variant	Exon 1 of 10	5	NM_001136506.2	ENSP00000480336.1
SLC22A24	ENST00000417740.5	c.-407A>G		5_prime_UTR_variant	Exon 1 of 10	5		ENSP00000396586.1
SLC22A24	ENST00000326192.5	c.-407A>G		5_prime_UTR_variant	Exon 1 of 4	1		ENSP00000321549.5

Frequencies

GnomAD3 genomes AF: 0.761 AC: 115611 AN: 151996 Hom.: 45548 Cov.: 31

Gnomad AFR AF: 0.537

Gnomad AMI AF: 0.799

Gnomad AMR AF: 0.830

Gnomad ASJ AF: 0.775

Gnomad EAS AF: 0.902

Gnomad SAS AF: 0.843

Gnomad FIN AF: 0.882

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.843

Gnomad OTH AF: 0.796

GnomAD4 exome AF: 0.830 AC: 4255 AN: 5124 Hom.: 1785 Cov.: 0 AF XY: 0.846 AC XY: 2195 AN XY: 2594

African (AFR) AF: 0.487 AC: 116 AN: 238

American (AMR) AF: 0.848 AC: 112 AN: 132

Ashkenazi Jewish (ASJ) AF: 0.811 AC: 198 AN: 244

East Asian (EAS) AF: 0.912 AC: 217 AN: 238

South Asian (SAS) AF: 0.862 AC: 50 AN: 58

European-Finnish (FIN) AF: 0.899 AC: 196 AN: 218

Middle Eastern (MID) AF: 0.821 AC: 23 AN: 28

European-Non Finnish (NFE) AF: 0.848 AC: 3062 AN: 3612

Other (OTH) AF: 0.789 AC: 281 AN: 356

GnomAD4 genome AF: 0.760 AC: 115644 AN: 152114 Hom.: 45553 Cov.: 31 AF XY: 0.763 AC XY: 56745 AN XY: 74358

African (AFR) AF: 0.536 AC: 22214 AN: 41442

American (AMR) AF: 0.831 AC: 12702 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.775 AC: 2692 AN: 3472

East Asian (EAS) AF: 0.902 AC: 4673 AN: 5182

South Asian (SAS) AF: 0.843 AC: 4053 AN: 4806

European-Finnish (FIN) AF: 0.882 AC: 9348 AN: 10602

Middle Eastern (MID) AF: 0.755 AC: 222 AN: 294

European-Non Finnish (NFE) AF: 0.843 AC: 57346 AN: 68002

Other (OTH) AF: 0.789 AC: 1665 AN: 2110

Alfa AF: 0.812 Hom.: 63837

Bravo AF: 0.750

Asia WGS AF: 0.825 AC: 2870 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	4.3
DANN	Benign	0.76
PhyloP100		0.46
PromoterAI		0.00010	Neutral
Mutation Taster		=300/0	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: rs1939747; hg19: chr11-62911658;