2-218384290-C-T

Variant names:

• chr2-218384290-C-T
• rs2276631
• NM_000578.4:c.198C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_000578.4(SLC11A1):​c.198C>T​(p.Phe66Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 1,607,394 control chromosomes in the GnomAD database, including 54,268 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

• Frequency:
  • Genomes: 𝑓 0.23 (4358 hom., cov: 32)
  • Exomes 𝑓: 0.26 (49910 hom.)
• Consequence: SLC11A1 NM_000578.4 synonymous
• Clinical Significance: risk factor no assertion criteria provided O:1
• Conservation: PhyloP100: 0.710
• Publications: 49 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BP7: Synonymous conserved (PhyloP=0.71 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000578.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC11A1	NM_000578.4	MANE Select	c.198C>T	p.Phe66Phe	synonymous	Exon 3 of 15	NP_000569.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC11A1	ENST00000233202.11	TSL:1 MANE Select	c.198C>T	p.Phe66Phe	synonymous	Exon 3 of 15	ENSP00000233202.6
	SLC11A1	ENST00000354352.9	TSL:1	n.198C>T		non_coding_transcript_exon	Exon 3 of 16	ENSP00000346320.5
	SLC11A1	ENST00000468221.5	TSL:1	n.1678C>T		non_coding_transcript_exon	Exon 2 of 13

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35352 AN: 152094 Hom.: 4355 Cov.: 32

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.199

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.253

GnomAD2 exomes AF: 0.235 AC: 58512 AN: 249308 AF XY: 0.231

Gnomad AFR exome AF: 0.169

Gnomad AMR exome AF: 0.304

Gnomad ASJ exome AF: 0.244

Gnomad EAS exome AF: 0.114

Gnomad FIN exome AF: 0.254

Gnomad NFE exome AF: 0.267

Gnomad OTH exome AF: 0.266

GnomAD4 exome AF: 0.257 AC: 374160 AN: 1455182 Hom.: 49910 Cov.: 32 AF XY: 0.253 AC XY: 183007 AN XY: 723982

African (AFR) AF: 0.169 AC: 5629 AN: 33332

American (AMR) AF: 0.306 AC: 13571 AN: 44396

Ashkenazi Jewish (ASJ) AF: 0.245 AC: 6368 AN: 25964

East Asian (EAS) AF: 0.128 AC: 5078 AN: 39530

South Asian (SAS) AF: 0.122 AC: 10452 AN: 85610

European-Finnish (FIN) AF: 0.250 AC: 13323 AN: 53256

Middle Eastern (MID) AF: 0.240 AC: 1376 AN: 5732

European-Non Finnish (NFE) AF: 0.274 AC: 303777 AN: 1107382

Other (OTH) AF: 0.243 AC: 14586 AN: 59980

GnomAD4 genome AF: 0.232 AC: 35376 AN: 152212 Hom.: 4358 Cov.: 32 AF XY: 0.231 AC XY: 17163 AN XY: 74402

African (AFR) AF: 0.178 AC: 7403 AN: 41552

American (AMR) AF: 0.289 AC: 4410 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.251 AC: 871 AN: 3472

East Asian (EAS) AF: 0.121 AC: 623 AN: 5164

South Asian (SAS) AF: 0.121 AC: 585 AN: 4828

European-Finnish (FIN) AF: 0.246 AC: 2606 AN: 10606

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.266 AC: 18078 AN: 67992

Other (OTH) AF: 0.253 AC: 533 AN: 2110

Alfa AF: 0.256 Hom.: 15385

Bravo AF: 0.237

Asia WGS AF: 0.123 AC: 427 AN: 3478

ClinVar

Significance: risk factor

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Mycobacterium tuberculosis, susceptibility to infection by Other:1

Aug 23, 2005

OMIM

Significance: risk factor

Review Status: no assertion criteria provided

Collection Method: literature only

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.54
BayesDel_noAF	Benign	-0.27
CADD	Benign	12
DANN	Benign	0.87
PhyloP100		0.71
Mutation Taster		=291/9	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs2276631; hg19: chr2-219249013; COSMIC: COSV51915749; COSMIC: COSV51915749;