2-218387654-C-T

Position:

• chr2-218387654-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000578.4(SLC11A1):​c.639+22C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 1,612,634 control chromosomes in the GnomAD database, including 50,972 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 0.21 (3717 hom., cov: 32)
  • Exomes 𝑓: 0.25 (47255 hom.)
• Consequence: SLC11A1 NM_000578.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0890

Genes affected

SLC11A1 (HGNC:10907): (solute carrier family 11 member 1) This gene is a member of the solute carrier family 11 (proton-coupled divalent metal ion transporters) family and encodes a multi-pass membrane protein. The protein functions as a divalent transition metal (iron and manganese) transporter involved in iron metabolism and host resistance to certain pathogens. Mutations in this gene have been associated with susceptibility to infectious diseases such as tuberculosis and leprosy, and inflammatory diseases such as rheumatoid arthritis and Crohn disease. Alternatively spliced variants that encode different protein isoforms have been described but the full-length nature of only one has been determined. [provided by RefSeq, Jul 2008]

SLC11A1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC11A1	NM_000578.4	c.639+22C>T		intron_variant		ENST00000233202.11	NP_000569.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC11A1	ENST00000233202.11	c.639+22C>T		intron_variant		1	NM_000578.4	ENSP00000233202.6

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32210 AN: 152064 Hom.: 3716 Cov.: 32

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.201

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.0879

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.234

GnomAD3 exomes AF: 0.215 AC: 54147 AN: 251264 Hom.: 6388 AF XY: 0.216 AC XY: 29371 AN XY: 135786

Gnomad AFR exome AF: 0.126

Gnomad AMR exome AF: 0.211

Gnomad ASJ exome AF: 0.247

Gnomad EAS exome AF: 0.0838

Gnomad SAS exome AF: 0.133

Gnomad FIN exome AF: 0.244

Gnomad NFE exome AF: 0.263

Gnomad OTH exome AF: 0.259

GnomAD4 exome AF: 0.249 AC: 363045 AN: 1460452 Hom.: 47255 Cov.: 33 AF XY: 0.245 AC XY: 178265 AN XY: 726610

Gnomad4 AFR exome AF: 0.129

Gnomad4 AMR exome AF: 0.216

Gnomad4 ASJ exome AF: 0.248

Gnomad4 EAS exome AF: 0.0818

Gnomad4 SAS exome AF: 0.133

Gnomad4 FIN exome AF: 0.240

Gnomad4 NFE exome AF: 0.269

Gnomad4 OTH exome AF: 0.238

GnomAD4 genome AF: 0.212 AC: 32213 AN: 152182 Hom.: 3717 Cov.: 32 AF XY: 0.209 AC XY: 15585 AN XY: 74394

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.232

Gnomad4 ASJ AF: 0.253

Gnomad4 EAS AF: 0.0885

Gnomad4 SAS AF: 0.131

Gnomad4 FIN AF: 0.239

Gnomad4 NFE AF: 0.262

Gnomad4 OTH AF: 0.235

Alfa AF: 0.247 Hom.: 7210

Bravo AF: 0.210

Asia WGS AF: 0.122 AC: 423 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.5
DANN	Benign	0.65

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: rs2290708; hg19: chr2-219252377; COSMIC: COSV51915504; COSMIC: COSV51915504;