chr2-218385280-G-C

Variant names:

• chr2-218385280-G-C
• rs3731865
• NM_000578.4:c.393+14G>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.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
• Publications: 82 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
• Mycobacterium tuberculosis, susceptibility

  Inheritance: AD Classification: LIMITED Submitted by: PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC11A1	NM_000578.4	MANE Select	c.393+14G>C		intron	N/A	NP_000569.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC11A1	ENST00000233202.11	TSL:1 MANE Select	c.393+14G>C		intron	N/A	ENSP00000233202.6	P49279-1
	SLC11A1	ENST00000354352.9	TSL:1	n.393+14G>C		intron	N/A	ENSP00000346320.5	Q9HBK0
	SLC11A1	ENST00000468221.5	TSL:1	n.2654+14G>C		intron	N/A

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

GnomAD2 exomes AF: 0.233 AC: 58550 AN: 250866 AF XY: 0.231

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 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

African (AFR) AF: 0.0915 AC: 3061 AN: 33470

American (AMR) AF: 0.305 AC: 13643 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.247 AC: 6458 AN: 26104

East Asian (EAS) AF: 0.129 AC: 5105 AN: 39672

South Asian (SAS) AF: 0.122 AC: 10554 AN: 86236

European-Finnish (FIN) AF: 0.261 AC: 13931 AN: 53330

Middle Eastern (MID) AF: 0.257 AC: 1482 AN: 5762

European-Non Finnish (NFE) AF: 0.280 AC: 310827 AN: 1111438

Other (OTH) AF: 0.244 AC: 14716 AN: 60372

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

African (AFR) AF: 0.0990 AC: 4116 AN: 41560

American (AMR) AF: 0.283 AC: 4334 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.251 AC: 870 AN: 3466

East Asian (EAS) AF: 0.121 AC: 627 AN: 5178

South Asian (SAS) AF: 0.120 AC: 581 AN: 4834

European-Finnish (FIN) AF: 0.258 AC: 2730 AN: 10598

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.271 AC: 18430 AN: 68000

Other (OTH) AF: 0.241 AC: 508 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.82
DANN	Benign	0.53
PhyloP100		-0.82
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: rs3731865; hg19: chr2-219250003; COSMIC: COSV51918538; COSMIC: COSV51918538;