2-218385280-G-C

Position:

• chr2-218385280-G-C

Variant summary

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

The NM_000578.4(SLC11A1):​c.393+14G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 1,613,326 control chromosomes in the GnomAD database, including 55,575 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 (3990 hom., cov: 33)
  • Exomes 𝑓: 0.26 (51585 hom.)
• Consequence: SLC11A1 NM_000578.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.823

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC11A1	NM_000578.4	c.393+14G>C		intron_variant		ENST00000233202.11	NP_000569.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC11A1	ENST00000233202.11	c.393+14G>C		intron_variant		1	NM_000578.4	ENSP00000233202.6

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32454 AN: 152124 Hom.: 3987 Cov.: 33

Gnomad AFR AF: 0.0994

Gnomad AMI AF: 0.199

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.240

GnomAD3 exomes AF: 0.233 AC: 58550 AN: 250866 Hom.: 7563 AF XY: 0.231 AC XY: 31297 AN XY: 135646

Gnomad AFR exome AF: 0.0897

Gnomad AMR exome AF: 0.304

Gnomad ASJ exome AF: 0.246

Gnomad EAS exome AF: 0.114

Gnomad SAS exome AF: 0.121

Gnomad FIN exome AF: 0.265

Gnomad NFE exome AF: 0.273

Gnomad OTH exome AF: 0.267

GnomAD4 exome AF: 0.260 AC: 379777 AN: 1461084 Hom.: 51585 Cov.: 33 AF XY: 0.256 AC XY: 185923 AN XY: 726854

Gnomad4 AFR exome AF: 0.0915

Gnomad4 AMR exome AF: 0.305

Gnomad4 ASJ exome AF: 0.247

Gnomad4 EAS exome AF: 0.129

Gnomad4 SAS exome AF: 0.122

Gnomad4 FIN exome AF: 0.261

Gnomad4 NFE exome AF: 0.280

Gnomad4 OTH exome AF: 0.244

GnomAD4 genome AF: 0.213 AC: 32467 AN: 152242 Hom.: 3990 Cov.: 33 AF XY: 0.212 AC XY: 15814 AN XY: 74422

Gnomad4 AFR AF: 0.0990

Gnomad4 AMR AF: 0.283

Gnomad4 ASJ AF: 0.251

Gnomad4 EAS AF: 0.121

Gnomad4 SAS AF: 0.120

Gnomad4 FIN AF: 0.258

Gnomad4 NFE AF: 0.271

Gnomad4 OTH AF: 0.241

Alfa AF: 0.181 Hom.: 590

Bravo AF: 0.215

Asia WGS AF: 0.117 AC: 405 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.82
DANN	Benign	0.53

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: rs3731865; hg19: chr2-219250003; COSMIC: COSV51918538; COSMIC: COSV51918538;