2-218387654-C-T

Variant names:

• chr2-218387654-C-T
• rs2290708
• NM_000578.4:c.639+22C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 24 publications found

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 Gene-Disease associations (from GenCC):

• cystic fibrosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SLC11A1	NM_000578.4	c.639+22C>T		intron_variant	Intron 7 of 14	ENST00000233202.11	NP_000569.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC11A1	ENST00000233202.11	c.639+22C>T		intron_variant	Intron 7 of 14	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

GnomAD2 exomes AF: 0.215 AC: 54147 AN: 251264 AF XY: 0.216

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 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

African (AFR) AF: 0.129 AC: 4299 AN: 33450

American (AMR) AF: 0.216 AC: 9676 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.248 AC: 6468 AN: 26112

East Asian (EAS) AF: 0.0818 AC: 3244 AN: 39680

South Asian (SAS) AF: 0.133 AC: 11471 AN: 86212

European-Finnish (FIN) AF: 0.240 AC: 12837 AN: 53408

Middle Eastern (MID) AF: 0.256 AC: 1452 AN: 5678

European-Non Finnish (NFE) AF: 0.269 AC: 299220 AN: 1110852

Other (OTH) AF: 0.238 AC: 14378 AN: 60352

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

African (AFR) AF: 0.135 AC: 5596 AN: 41528

American (AMR) AF: 0.232 AC: 3555 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.253 AC: 877 AN: 3470

East Asian (EAS) AF: 0.0885 AC: 458 AN: 5176

South Asian (SAS) AF: 0.131 AC: 635 AN: 4830

European-Finnish (FIN) AF: 0.239 AC: 2523 AN: 10578

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.262 AC: 17802 AN: 67988

Other (OTH) AF: 0.235 AC: 497 AN: 2116

Alfa AF: 0.246 Hom.: 9709

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
PhyloP100		0.089
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: rs2290708; hg19: chr2-219252377; COSMIC: COSV51915504; COSMIC: COSV51915504;