chr2-218387907-C-T

Variant names:

• chr2-218387907-C-T
• rs17221959
• NM_000578.4:c.747C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_000578.4(SLC11A1):​c.747C>T​(p.Gly249Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0598 in 1,607,688 control chromosomes in the GnomAD database, including 5,283 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.12 (1811 hom., cov: 32)
  • Exomes 𝑓: 0.054 (3472 hom.)
• Consequence: SLC11A1 NM_000578.4 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -6.94
• Publications: 35 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 2-218387907-C-T is Benign according to our data. Variant chr2-218387907-C-T is described in ClinVar as Benign. ClinVar VariationId is 3055354.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-6.94 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) 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.747C>T	p.Gly249Gly	synonymous	Exon 8 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.747C>T	p.Gly249Gly	synonymous	Exon 8 of 15	ENSP00000233202.6
	SLC11A1	ENST00000354352.9	TSL:1	n.*329C>T		non_coding_transcript_exon	Exon 9 of 16	ENSP00000346320.5
	SLC11A1	ENST00000468221.5	TSL:1	n.3008C>T		non_coding_transcript_exon	Exon 6 of 13

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17530 AN: 151954 Hom.: 1808 Cov.: 32

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.0683

Gnomad ASJ AF: 0.0378

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.0338

Gnomad MID AF: 0.0673

Gnomad NFE AF: 0.0424

Gnomad OTH AF: 0.0912

GnomAD2 exomes AF: 0.0702 AC: 16603 AN: 236632 AF XY: 0.0667

Gnomad AFR exome AF: 0.286

Gnomad AMR exome AF: 0.0675

Gnomad ASJ exome AF: 0.0360

Gnomad EAS exome AF: 0.106

Gnomad FIN exome AF: 0.0297

Gnomad NFE exome AF: 0.0401

Gnomad OTH exome AF: 0.0537

GnomAD4 exome AF: 0.0539 AC: 78519 AN: 1455616 Hom.: 3472 Cov.: 32 AF XY: 0.0544 AC XY: 39360 AN XY: 723672

African (AFR) AF: 0.294 AC: 9823 AN: 33412

American (AMR) AF: 0.0644 AC: 2800 AN: 43446

Ashkenazi Jewish (ASJ) AF: 0.0402 AC: 1040 AN: 25848

East Asian (EAS) AF: 0.0791 AC: 3118 AN: 39424

South Asian (SAS) AF: 0.0956 AC: 8155 AN: 85276

European-Finnish (FIN) AF: 0.0299 AC: 1578 AN: 52778

Middle Eastern (MID) AF: 0.0631 AC: 363 AN: 5752

European-Non Finnish (NFE) AF: 0.0428 AC: 47485 AN: 1109566

Other (OTH) AF: 0.0692 AC: 4157 AN: 60114

GnomAD4 genome AF: 0.115 AC: 17560 AN: 152072 Hom.: 1811 Cov.: 32 AF XY: 0.115 AC XY: 8574 AN XY: 74368

African (AFR) AF: 0.285 AC: 11822 AN: 41462

American (AMR) AF: 0.0681 AC: 1041 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0378 AC: 131 AN: 3468

East Asian (EAS) AF: 0.109 AC: 560 AN: 5154

South Asian (SAS) AF: 0.108 AC: 523 AN: 4824

European-Finnish (FIN) AF: 0.0338 AC: 358 AN: 10592

Middle Eastern (MID) AF: 0.0690 AC: 20 AN: 290

European-Non Finnish (NFE) AF: 0.0424 AC: 2881 AN: 67978

Other (OTH) AF: 0.0897 AC: 189 AN: 2106

Alfa AF: 0.0788 Hom.: 513

Bravo AF: 0.125

Asia WGS AF: 0.114 AC: 399 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

SLC11A1-related disorder Benign:1

Jan 22, 2024

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	4.9
DANN	Benign	0.93
PhyloP100		-6.9
Mutation Taster		=99/1	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: rs17221959; hg19: chr2-219252630; COSMIC: COSV107231850; COSMIC: COSV107231850;