rs17235409

Variant names:

• chr2-218395009-G-A
• rs17235409
• NM_000578.4:c.1627G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-218395009-G-A
• chr2-218395009-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000578.4(SLC11A1):​c.1627G>A​(p.Asp543Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0284 in 1,609,430 control chromosomes in the GnomAD database, including 1,304 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.041 (195 hom., cov: 33)
  • Exomes 𝑓: 0.027 (1109 hom.)
• Consequence: SLC11A1 NM_000578.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1 O:1
• Conservation: PhyloP100: -0.624
• Publications: 168 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 (MetaRNN=0.0014781058).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC11A1	NM_000578.4	c.1627G>A	p.Asp543Asn	missense_variant	Exon 15 of 15	ENST00000233202.11	NP_000569.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC11A1	ENST00000233202.11	c.1627G>A	p.Asp543Asn	missense_variant	Exon 15 of 15	1	NM_000578.4	ENSP00000233202.6

Frequencies

GnomAD3 genomes AF: 0.0412 AC: 6263 AN: 152186 Hom.: 197 Cov.: 33

Gnomad AFR AF: 0.0632

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0638

Gnomad ASJ AF: 0.0118

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.0639

Gnomad FIN AF: 0.0225

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0180

Gnomad OTH AF: 0.0411

GnomAD2 exomes AF: 0.0491 AC: 11852 AN: 241194 AF XY: 0.0454

Gnomad AFR exome AF: 0.0621

Gnomad AMR exome AF: 0.114

Gnomad ASJ exome AF: 0.0145

Gnomad EAS exome AF: 0.139

Gnomad FIN exome AF: 0.0216

Gnomad NFE exome AF: 0.0197

Gnomad OTH exome AF: 0.0337

GnomAD4 exome AF: 0.0271 AC: 39430 AN: 1457126 Hom.: 1109 Cov.: 32 AF XY: 0.0273 AC XY: 19758 AN XY: 724476

African (AFR) AF: 0.0610 AC: 2035 AN: 33386

American (AMR) AF: 0.104 AC: 4599 AN: 44258

Ashkenazi Jewish (ASJ) AF: 0.0138 AC: 358 AN: 26004

East Asian (EAS) AF: 0.118 AC: 4689 AN: 39584

South Asian (SAS) AF: 0.0531 AC: 4535 AN: 85460

European-Finnish (FIN) AF: 0.0198 AC: 1045 AN: 52730

Middle Eastern (MID) AF: 0.0353 AC: 203 AN: 5758

European-Non Finnish (NFE) AF: 0.0179 AC: 19836 AN: 1109726

Other (OTH) AF: 0.0354 AC: 2130 AN: 60220

GnomAD4 genome AF: 0.0411 AC: 6266 AN: 152304 Hom.: 195 Cov.: 33 AF XY: 0.0428 AC XY: 3185 AN XY: 74470

African (AFR) AF: 0.0632 AC: 2625 AN: 41556

American (AMR) AF: 0.0636 AC: 973 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0118 AC: 41 AN: 3472

East Asian (EAS) AF: 0.144 AC: 746 AN: 5168

South Asian (SAS) AF: 0.0634 AC: 306 AN: 4830

European-Finnish (FIN) AF: 0.0225 AC: 239 AN: 10624

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0180 AC: 1226 AN: 68036

Other (OTH) AF: 0.0406 AC: 86 AN: 2116

Alfa AF: 0.0278 Hom.: 467

Bravo AF: 0.0458

TwinsUK AF: 0.0178 AC: 66

ALSPAC AF: 0.0169 AC: 65

ESP6500AA AF: 0.0611 AC: 269

ESP6500EA AF: 0.0183 AC: 157

ExAC AF: 0.0454 AC: 5507

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1 Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

Cystic fibrosis Uncertain:1

Apr 01, 2023

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: research

- -

Buruli ulcer, susceptibility to Other:1

Apr 01, 2006

OMIM

Significance: risk factor

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	3.0
DANN	Benign	0.96
DEOGEN2	Benign	0.23	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.054	N
LIST_S2	Benign	0.50	T
MetaRNN	Benign	0.0015	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.6	L
PhyloP100		-0.62
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.49	N
REVEL	Benign	0.0050
Sift	Benign	0.057	T
Sift4G	Benign	0.097	T
Polyphen		0.078	B
Vest4		0.019
MPC		0.12
ClinPred		0.0029	T
GERP RS		-0.51
Varity_R		0.048
gMVP		0.14
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: rs17235409; hg19: chr2-219259732; COSMIC: COSV51918328; COSMIC: COSV51918328;